Inspiration

Kwok was diagnosed with glaucoma in 2023, experiencing rapid vision loss post-diagnosis. He manages his condition with subsidized eye drops (HKD$300/month) and quarterly hospital check-ups. Despite the convenience and effectiveness of the drops in regulating eye pressure, they fail during occasional severe pain. Kwok’s experience is really inspiring. In this interview, we learnt the hardships patients have to face in their daily lives, including sensory adaptation and tweaks of life routines. He also mentioned the hindrance and difficulties of current treatments, checkups and medications. This inspired us to solve specific problems of patients with our product, with information given by Kwok.

Implementation

We have taken advice from Kwok and conducted a number of implementations accordingly. Science wise, as Kwok expressed difficulties of some patients in affording the drugs, we have started researching on commercial ways to lower the product price (Stage IV: into the market), as well as planning for simulated experiments to simulate our product’s IOP decrease ability, compared to commercially available drugs. In our education programmes, we have also taken a lot of advice from Kwok. In our courses (PCMS & HKPA), we had extensive courses and lessons on the hardships of glaucoma and visually impaired patients.

Implication

Through this interview, we found out that the current market really needs a drug that patients can experience the drug’s efficiency during the treatment. Besides, we realised that patients in Hong Kong are generally not well and holistically supported. Even if the systematic factors are well supported (medication price, check-up waiting time), they still severely lack a sense of support and inclusivity in our society. This encourages us to host a series of seminars and workshops to maximize our impact in making a difference in our society, fostering a more inclusive and caring environment for the visually impaired individuals.

Inspiration

In this meeting with glaucoma patients, we have known that patients are always annoyed by the frequency of taking irritating eye drops. They may need to drip at most 13 eye drops a day. After questioning and understanding every patient’s needs, it is suggested to minimise the side effects of the drug. Additionally, some patients pointed out that as they face difficulties in aiming their eyes, they often waste a lot of eye drops. Adding an extra assistive device might be an ideal eye drop bottle design, which would reduce the ineffective drops of the drug.

Implementation

We have taken advice from the patients in HKBU and conducted a number of implementations accordingly. As they expressed discomfort with the side effects in glaucoma drugs, we have been investigating the irritation level of our proposed drug. Additionally, as many of them reported their difficulties in affording treatments and drugs, we have been conducting more interviews with marketing professors about how to better address the realistic needs of patients, as well as conducting more thorough research on stage 4: into the market.

Implication

Through this interview, we found out that patients in Hong Kong are generally not well and holistically supported. Despite the well supported support from local non-profit organisations, they are still facing an average of 31 weeks of check-up waiting times in public hospitals and high medication prices in private ones. This motivates us to hold an array of workshops to increase our impact and preserve a supportive atmosphere for people with visual impairments.

Inspiration

In this meeting with glaucoma patients, we have known that patients are always annoyed by the frequency of taking irritating eye drops. They may need to drip at most 13 eye drops a day. After questioning and understanding every patient’s needs, it is suggested to minimise the side effects of the drug. Additionally, some patients pointed out that as they face difficulties in aiming their eyes, they often waste a lot of eye drops. Adding an extra assistive device might be an ideal eye drop bottle design, which would reduce the ineffective drops of the drug.

Implementation

We have taken advice from the patients in HKBU and conducted a number of implementations accordingly. As they expressed discomfort with the side effects in glaucoma drugs, we have been investigating the irritation level of our proposed drug. Additionally, as many of them reported their difficulties in affording treatments and drugs, we have been conducting more interviews with marketing professors about how to better address the realistic needs of patients, as well as conducting more thorough research on stage 4: into the market.

Implication

Through this interview, we found out that patients in Hong Kong are generally not well and holistically supported. Despite the well supported support from local non-profit organisations, they are still facing an average of 31 weeks of check-up waiting times in public hospitals and high medication prices in private ones. This motivates us to hold an array of workshops to increase our impact and preserve a supportive atmosphere for people with visual impairments.

Inspiration

Prof. Crowston mentioned that we have to make sure the drug is safe but considering we cannot do any animal test, Prof. Crowston suggested we check the molecules of the drug molecules which are already used in other drugs to make sure they’re safe. Prof. Crowston told us that lowering IOP still works for normal-tension glaucoma patients so we may need to tweak the ratio of the drugs in fusion protein. Prof. Crowston also mentioned that liposome work for drug delivery but are very short lived. Prof. Crowston thinks we have a solid interesting project, but he’d ask what the really smart, innovative part of the project is. Using fusion proteins is clever, solving different problems is still very impressive but how do we get the spark for the judges to think it’s a really smart and good idea?According to Dr. Crowston, too many ideas will dilute the project, just emphasise on the spark. Prof. Crowston also emphasized that our approach is so well done already but we need to fine tune the presentation to highlight the wow factor more, to make our project look cleverer. At last, Prof. Crowston believes that our project has a potential to be launched to the market.

Implementation

For the safety of our drug, we will conduct toxicity and further computational modeling tests to prove its safety in the human body. For the ratio of our drugs, we have sought advice from professionals. However, we were told that it would be hard to accurately estimate the ratio for patients as the ratio of drugs may vary between different glaucoma patients. Critically, our research indicates that overdosing of either the FT or BC component does not trigger negative side effects. We have figured the spark of our project would be about the unique ability of our drug to target RGC apoptosis in a non-invasive manner. The dual- targeting of our drug also allows it to achieve a comprehensive therapeutic effect of open angle glaucoma.

Implication

After the interview, we could ensure our drug has a quite rigorous scientific pathway and the way we present this project is well organized. This serves as a confirmation on the process of the passing down of knowledge, in which we applied in our various activities. We aim to continue our engagement with different stakeholders, and constantly improve our method of knowledge transmission, so that we can more effectively convey our messages of knowledge and awareness related to SynBio and Glaucoma.

Inspiration

In the interview with Dr. Wong, we understand that there are no reliable biomarkers for diagnosing glaucoma which means there are no accurate standards to check if one has glaucoma. Also, the bioavailability of eye drops is around 10%. Aqueous solution can’t pass through the first layer and oil can’t pass through the second layer. The possibility of the eyedrop to get into the layer with RGCs will be so low that our eye drops can’t reach the targeted cell to function properly. Instead of trying to achieve 3 aspects of scientific breakthroughs, we should focus on one and provide in-depth elaborations on the topic. We should also consider and research on reducing side-effects, lowering the cost and making a simpler drug to apply as directions of our project.

This interview has inspired us to focus on the therapeutic side and provide in-depth elaborations on the topic. Apart from pursuing excellence of the drug effect, we should also consider and research on reducing side-effects, lowering the cost and making a simpler drug to apply as directions of our project. It is suggested to opt for Non-Governmental Organisations (NGOs) for reaching different types of stakeholders accordingly. As hardships of glaucoma patients and the sociological aspect of glaucoma are also highly valuable, we should also strive to promote and spread awareness of them. Social media should also be used to maximize the reach of our project.

Implementation

Science wise, we should perform research on developing a neural protection drug and come up with viable chemicals to synthesize the drug. The idea of developing a test kit should be removed. Methods to lower the side-effects of the drug are also being researched. Possible directions may be finding out the cause of side effects in current drugs on the market, and finding chemicals that can lower the side effects. We went on to research and apply TAT to our project, a peptide that can double the bioavailability of our drug.

For outreach, we went on to connect with NGOs for event collaborations. (Hong Kong Playground Association & Hong Kong Blind Union & Hong Kong Glaucoma Patients’ Association) The materials in our activities should include more sociological information and hardships from patients, so that we can alleviate the lack of awareness in glaucoma patients among the society. We also produced our first of many minifilms.

Implication

Dr. Wong has also mentioned that the general public have some misunderstandings on glaucoma such as the misconception that elders are at higher risk of getting glaucoma. In fact, age is not a determining factor in the tendency of getting glaucoma, the age of 60 or above is the group with highest risk simply due to their prolonged time to allow glaucoma - a chronic disease to develop. After the interview, we understand that it is best for us to tailor the content of our educational programmes according to the existing knowledge and common misconception on glaucoma by the general public. Through in-depth analysis of data we have collected, we can obtain an insight into the view on this disease of different stakeholders. Hence, we should tailor-make our content to suit the demand from them, filling gaps and misunderstandings of their cognition, so that we can reach our maximum impact with the most cost-effective and efficient direction of development in terms of our outreach programmes.

Inspiration

The exchange with HG Tokyo provided significant inspiration for refining our approach to several aspects of the iGEM competition:

Human Practices Integration: We were inspired by HG Tokyo's deep integration of stakeholder feedback, particularly their planned face-to-face engagement with Jabara farmers, which serves as a model for addressing project-specific ethical and social considerations in a meaningful way.

Education & Audience Targeting: HG Tokyo's challenge in engaging adult audiences highlighted the importance of demographic-specific strategies. Their successful international university collaborations (e.g., with Imperial and Cambridge) inspired us to consider similar global partnerships for our educational events.

Marketing & Public Perception: Their team's advice to interview pharmaceutical companies provided a clear, actionable pathway for understanding how to overcome market challenges and public skepticism surrounding genetically modified treatments, a key hurdle for our project.

Wiki Presentation: The discussion on moving beyond a simple list of activities towards a narrative that shows how human practices shaped the project inspired us to rethink our wiki structure to better demonstrate integration and impact.

Implementation

Stakeholder Engagement: We will act on the advice to contact local pharmacies and pharmaceutical companies to conduct interviews focused on marketing strategies for GMO-based treatments and navigating regulatory hurdles. This is crucial for HP Stage IV - Into the market.

Education Program Design: We will tailor our upcoming seminar with Chinese University of Hong Kong biochemistry freshmen to emphasize not just knowledge transfer but also the mutual exchange of innovation and project-building experience, as inspired by the meeting discussion. We will also consider contacting HG Tokyo for further oversea educational activities. We are also inspired to host awareness-raising events at school to amplify our project.

Project Narrative: In constructing our wiki, we will implement a more integrated structure for the Human Practices section, using a timeline or subsections to clearly visualise how feedback from interviews and events directly influenced our project's development and direction. We will also try to build a more eye-catching and story-telling flow in our wiki page.

Collaboration: We will formally participate in HG Tokyo’s webinar on August 26th and will proceed with planning a mid-September international online meet-up to further discuss synthetic biology and project design.

Implication

The meeting implied that successful iGEM projects are built on continuous iteration based on diverse stakeholder input. HG Tokyo’s method of directly engaging with the source of their product (Jabara farmers) sets a high standard for responsible and ethical innovation. Furthermore, the discussion revealed that a common challenge among teams is effectively communicating complex science and addressing GMO concerns for public acceptance. This implies that a significant part of our human practice efforts should be dedicated to understanding and designing strategies for market integration and public communication, not just scientific validation. The emphasis on a two-way educational exchange with university students also implies that the value of an iGEM project lies not only in its output but in its capacity to inspire and educate peers at all levels.

Inspiration

Eye drops have clinical effectiveness yet possess various drawbacks (Short shelf-life, side effects, high price). Most patients follow doctors’ instructions. The main reason why some patients may not comply with taking eye drops on a regular basis is because of life schedules and laziness. This interview has inspired us to consider a more realistic and down-to-earth viewing angle in the ideal characteristic of our drug, based on the current needs of patients (bioavailability, side effects, invasiveness, dosage). This meeting has encouraged us to narrow down our scope and ambition, as we should take into consideration the realistic factors such as time, resources and difficulty of our original plans. In order to plan a better education activity, Dr. Yim and Dr. Yang have also suggested we consider the specific group of patients, as they also have a lack of knowledge towards glaucoma, eye health and biology.

Implementation

Science wise, it is suggested for us to perform further research on how to minimize side effects and increase bioavailability (carrier methods). We should also take the factor of cost into consideration. For Outreach, we should contact the Hong Kong Glaucoma Patient Association and investigate the possibilities of hosting educational workshops and interviews with patients and caretakers.

Implication

Throughout the interview, we realize the lack of awareness, knowledge of groups and the utmost importance to bear the responsibility of spreading related content to both the general public and more specific groups. It is suggested that we can make booths, and hand out leaflets to passersby or schoolmates. Therefore, we aim to collaborate with different schools to broaden our reach, maximize our impact with the most efficient efforts, as we hold events to teach students about basic information about glaucoma as we believe education is one of the most important elements to raise public awareness. Next, we wanted to deepen our understanding on what factors patients would consider when purchasing eyedrops. Therefore, we decided to interview more glaucoma patients.

Inspiration

In this meeting with glaucoma patients, we have known that patients are always annoyed by the frequency of taking eye drops. They may need to drip eyedrop almost six times a day. After questioning and understanding every patients’ needs, the modest frequency of using eye drops for patients is twice a day, once in the morning and once before bed as this frequency of using eye drops wouldn’t interrupt the patient’s daily schedule. On the other hand, our team members have also asked questions about the package of eyedrop. Several patients reported that the design of the cap that requires the patient's screw to open is not convenient for patients. Furthermore, some patients told us that sometimes they would waste some eye drops as they may not aim their eye perfectly.

Implementation

After the interview with glaucoma patients, our team members have done a lot of tests to ensure the low side effect profile. Including LABBBBBBBBBBBBBBBBBBBBBBB. We also are reminded, through this interview, to investigate the eyedrop intake interval of our product. Through tests like LABBBBBBBBBBBBBBBBBBBBBBBBB, we know more about how often patients should take our theoretical drug. These two are a crucial aspect for our product, regarding patients’ experience.

Implication

This interview is a sobering reminder that patients’ needs are often overlooked. In the aspects of doctors appointment waiting time, glaucoma education, information about glaucoma treatment types, are all poorly transmitted to patients. This allows us to outline our future education activities, with focus on creating content and events to promote the above-mentioned aspects in the life of patients. Subsequently, we strive to create a more inclusive and kind society to the blinds. This interview gave us specific scope to achieve so.

Inspiration

In this interview with HKGPA’s social workers, we have understood that patients association often invite ophthalmologists and glaucoma specialist to their centre to give talks. Ms. Chan mentioned that these talks indeed can provide updated informations to patents but the scale of the these activities is too small, so only patients can be benefitted. Mr. Yiu said that the general public is lack of the information about glaucoma. He said a lot of patients, especially those who are only diagnosed a short period are shocked by the speed at which this disease can deteriorate. Lack of public awareness is the main reason why the number of diagnosed patients has kept on increasing in recent years. There are not enough opportunities for the general public, no matter children, adults or elderly, to receive information about glaucoma and alternatively cannot understand how glaucoma can affect one’s life.

Implementation

After this interview, we realized that increasing public awareness is a mission for our outreach team. We decided to organize small scale educational activities first and conduct some questionnaires in order to collect advice and improve our activities next time. We first started from local students such as holding game booths, making board games and joining volunteering activities to teach students from 5 years old to 18 years old of ways to prevent glaucoma. After these activities, we plan to upscale the activities so the process can be more effective.

Implication

Social workers Miss Chan and Mr Yiu both mentioned the knowledge difference between patients, elders, and the general public. It seems that elders and patients have a less sophisticated channel to receive information regarding glaucoma and SynBio. This encourages us to focus more on engaging with patients and elders, narrowing the knowledge difference between them and the rest of the world. In this interview, they both mentioned that it is extremely crucial for patients and elders to be more informed , so that they can be empowered to face this disease and make informed medical and daily decisions.

Inspiration

He pointed out that decreasing IOP is possible which means our mindset is correct, but it may be a cliche idea for developing a drug soothing the deterioration of glaucoma. This interview inspired us to recall: what makes our project special? Is it more effective than other drugs? Adding some benefits compared to other drugs in the current market attracts more customers. Furthermore, Prof. Leung has also asked how we can convince local universities to collaborate with our team. We may need to reconsider the possibility of collaboration.

Implementation

After the interview with Prof. Leung, we did some more research on other eye-drop products in the market. We have found out that a large portion of current drugs usually only have one function. Therefore, this meeting has inspired us to make a multi-target eyedrop. Our eyedrop combines two fusion products, TAT-FWT and TAT-BC, targeting the high intraocular pressure in the eye and the apoptosis of retinal ganglion cells. We have used the cocktail theory to tackle both problems, combining 2 functions in one eye drop, making it unique from other eye drops that are currently available in the market.

Implication

After the meeting with Prof. Leung, our team is inspired to make a multi-target eyedrop product in order to reduce the frequency of patients using eyedrops. This meeting has changed our main direction of the project, turning it into a more meaningful one. Afterwards, we have also sent emails to several professors in Hong Kong, inviting them to collaborate with our team. Our team is able to use the laboratory of CUHK to do more advanced experiments with their equipment.

Inspiration

During this visit to their office, we introduced our project to their team including experienced iGEMers. LINK-SPIDER’s team members approved the main topic of the project, helping us to narrow down our project’s coverage. After introducing our educational events, Mr. Wang’s team suggested we widen the scope of our educational events, as we were only focusing on students and elderly in Hong Kong at that stage. Furthermore, they also recommended us to connect with more mainland professionals as we have less language barriers and mainland professionals are more accessible for our team. In the visit, we have also expressed our admiration to Mr. Wang of how he could turn an iGEM project into a real product. Mr. Wang has introduced his entrepreneurship journey, and mentioned we could make a business proposal for our future project’s development.

Implementation

In order to widen the scale of educational events, we wanted to organize some educational activities in mainland China. However, as Hong Kong and the mainland are currently using different communication systems, there are many obstacles to contacting patient associations or schools in the mainland. Even though there are numerous challenges, our educational team members change our target into online educational activities. We have posted several posts about glaucoma on XiaoHongShu. In addition to building connections with mainland professors, our students have organised a meeting with Prof. Chu Wai from Qingdao University in order to listen to more advice from several professionals. Our human practice members started to do research about the business proposal and made a draft of the business in July.

Implication

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Inspiration

Through the interview with Dr. Porciatti, we have understood that the idea of lowering IOP and protecting RGCs is possible. Dr. Porciatti has challenged the feasibility of eyedrop. Considering the number of layers and the size of the eye, the drug may not penetrate from the cornea all the way to the retina and reach the RGCs if we’re putting eyedrops on the top of the cornea. Furthermore, Dr. Porciatti has also mentioned that the drug may enter different vessels in the eyes and cause some unwanted effects. He suggested we do some research on the side effects which may be caused by the drug. Lastly, Dr. Porciatti recommended us to think of some of the limitations of the drug to show the judges that we have really thought about different aspects of the project.

Implementation

After the meeting with Dr. Porciatti, we have done some research on solving the problem of drugs reaching RGCs and entering into different vessels. As we have used TAT as a penetrating peptide to carry our drug to enter the RGCs. In our peptide TAT-BC, TAT brings BDNF and CDR1 to the RGCs. Also, we have done some research on the effects of our drugs when entering different vessels in the eye. It shows that both of our drugs show no harm to other vessels, some could even bring out positive effects.

Implication

After this meeting, we have ensured that our drug wouldn’t have brought out any negative effect on other vessels. Also, Dr. Porciatti recommended that we explore the shortcomings of our drug. He believed that presenting our shortcomings and methods to improve in our presentation in the judging session could demonstrate to the judges that we have brainstormed our drug comprehensively. After this interview with (...)

Inspiration

Dr. Chan provided us insights as to adjusting our direction of project, considering more factors of our drugs, and how we should approach each problem. We should approach the project based on a theoretical level (cellular level), though the realistic environment in our eyes will affect the performance of our drugs, it is best for us to remain on a cellular level, which is enough for the competition. The drug's cell penetration rate should also be taken into consideration. It is noted that there are drugs of similar properties on the market. It holds significant value to our project (focusing on their weaknesses) while also possessing a threat to our innovation. Market wise, there is not much we can do to reduce the cost of drugs, as it is directly related to the success rate of research of pharmaceutical companies.

Implementation

Science wise, there are several things we have implemented into our project after this interview. Firstly, we conducted research on how we can improve the penetration rate of drugs. We also looked into latanoprostene bunod, netarsudil, and fixed combination netarsudil-latanoprost, which are drugs of similar properties and theories with our project. Moreover, we performed more research on drugs of glaucoma to look for weaknesses for us to develop on, such as Brimonidine which is not yet implemented into humans. We also are considering nano-particles and photo-disruption methods (IV needed) as our drug carrier method. For outreach, we are enabled to expand our reach to wider regions. We are contacting professors in mainland China, as well as trying to reach out to social authorities in mainland China and the Taiwan region.

Implication

In this matured stage of our project, Dr. Chan enables us to keep extending our influence in different aspects. We should extend our reach to nearby regions with no language barrier (Mainland China and Taiwan Region), so that we can maximize our impact and influence. We should also contact social authorities of the underprivileged, as they lack knowledge about glaucoma and synthetic biology the most. After this interview with Dr. Chan, we wanted to know more about lab experiments, so we contacted Prof. Chu, who is Dr. Chan’s colleague.

Inspiration

In this meeting with Dr. Chu, he recommended us to do the Draize test which is commonly used to assess the potential for chemicals or substances to cause eye irritation or damage but the Draize test involved animals or living organisms. Eye drops could reach the RGCs by sliding down the surface of the eyeball instead of dripping it into the cornea. Dr. Chu told us that we don’t have to design the eyedrop to reach RGCs directly. He proposed that we could design the eye drop to reach other cells and further activate different reactions to protect RGCs so that there will not be an unwanted reaction if the drug is off target unless it is overdosed. Experiments done by Dr. Chu proved that using ultrasound to inject the drug is possible. But one of the downsides of this technique is that patients have to remain still during the process, so this is very hard for implementing this technique into clinical practice. Another downside is that the temperature of ultrasound may cause denaturation of the protein. Most optometrists do not want to use eye drop products which contain preservatives as some microorganisms may breed and also lead to side effects such as dryness, inflammation and itchiness of the eye.

Implementation

We will not be using the Draize test as we are not allowed to use living animals in our experiments. However, we have done different dry lab tests to test toxicity and allegenocinity, in order to test if any irritations will be caused by our eyedrops. We have done some research about our eyedrop reaching other eye structures. We have found that some structures might be able to activate neuroprotection or carry out positive effects. However, they could not directly stop the apoptosis of RGC and protect them which is what we are targeting in our project. Therefore, at the current stage, we are still working on the delivery of eyedrop to the RGCs.We will not be using ultrasound as our delivery method, as Dr. Chu mentioned that it required the patients to not blink for a period of time, which is not user friendly. Therefore, we will not consider using this method.

Implication

After this interview with Dr. Chu, our team members have started researching more information about the drug delivery of our drug. After we have communicated with Dr. Chu through email, we have the opportunity of doing some of the advanced experiments in Dr. Chu laboratory. In days of research, we have some ideas about drug delivery therefore we decided to interview Prof. Do from The Hong Kong Polytechnic University.

Inspiration

In the meeting, Prof. Do believes the idea of combining two drugs is good but it will increase the complexity at the same time. It is because the molecular size of the drug will be so large if the two drugs can only separate when it enters the eye. The molecular size of current drugs are only 200-800. The larger the drug, the harder it can enter the eye. One of the hardest obstacles to conquer in curing glaucoma is that drugs cannot enter the eye. Most treatments for curing eye diseases are using eye drop. Less than 5% of the drug can enter the eye by eye drop. Cancer drugs adopt targeted therapy to interfere with specific targeted molecules needed for carcinogenesis and tumor growth. Therefore, Prof. Do think we cannot remove all side effects caused by our eye drops. One thing we could do is to check the concentration of the drug. We hope to retain the accuracy and also prevent most unwanted side effects. For solubility and bioavailability, As our drug consists of two parts, we can try to dissolve the product into different solvent such as DMSO, ethanol and maybe water. We cannot choose to use a high concentration DMSO. Prof. Do’s laboratory sometimes uses Beta-cyclodextrin to improve the solubility of the compound. Beta-cyclodextrin is non-toxic to the human body. Prof. Do has also told us that RGC-5 is not a well cell line as people thought it was RGCs cell, but they further found out that RGC-5 is actually a photoreceptor cell so very few scientists used this cell line to do experiments.

Implementation

Prof. Do noted that typically only a small percentage of the drug in eye drops reaches the intended target. Even if some of the drug doesn't reach the target area, the therapeutic effect can still be achieved with the amount that does. To increase the probability of eye drops reaching the target, strategies such as increasing viscosity to prolong contact time, using permeation enhancers for better absorption, optimizing drop size, and ensuring formulation stability can be effective. Additionally, employing targeted delivery systems like nanoparticles and adjusting pH and osmolarity can further enhance delivery. Importantly, off-target effects are minimal and generally do not result in significant side effects, making the small doses used in eye drops manageable. We will also conduct pharmacokinetics tests to evaluate and optimize the delivery and efficacy of the formulation. To improve the solubility of eye drops, three effective strategies are the use of nanotechnology, pH adjustment, and stabilizers. Nanotechnology, such as utilizing nanoparticles or liposomes, can significantly increase the surface area and enhance the solubility of the active ingredients. Adjusting the pH of the formulation optimizes the solubility of the drug, ensuring better absorption and efficacy. Additionally, incorporating stabilizers helps maintain the integrity of the formulation while further enhancing solubility. By focusing on these approaches, the solubility of eye drop formulations can be effectively improved.

Implication

After this interview with Prof. Do, our team members have been working on exploring more dynamics of tissue in the eye and nanoparticles. We have read some of the papers that Prof. Chu Wai published. Therefore, we decided to interview the writer, Prof. Chu from Qingdao University.

Inspiration

In this meeting with Prof. Chu, we have mentioned our idea of designing a nanoparticle and she agreed with our approaches. Prof. Chu recommended us to design some antibodies. These antibodies can bind to some specific antigen in trabecular meshwork or RGCs. This is one way to prevent off-targeting. Prof. Chu thinks it is possible for TAT-FWT to be delivered but as the RGCs are in the back of the eye, Prof. Chu is quite concerned about the delivery of BC into the RGCs. Prof. Chu suggested we consider another delivery method apart from eye drop such as injection. Prof. Chu suggested that Schlemm canal is a more important tissue than trabecular meshwork. These two parts of tissue (Schlemm canal and trabecular meshwork) are connected and functioned together. Trabecular meshwork is in the inner part of the eye and the Schlemm canal is beneath the trabecular meshwork and located in the outer part of the eye. Schlemm canal can be a tissue for us to target. The trabecular meshwork filters the aqueous humor but ECM is beneath the Schlemm canal and the retina cell layer. Trabecular meshwork has three different layers so the GCT layer may be more important than other layers in the trabecular meshwork. Compared to trabecular meshwork, RGC regeneration is very difficult. Trabecular meshwork is much easier like cornea. We could use some stem cell method to regenerate the tissue and reconstruct the aqueous humor outflow. But for RGC, they have to transfer signals into our brain for our vision. The most difficult thing is projection. Once the RGC cells begin to die, the axon loses gradually. So far we have several methods by using stem cells like mesenchymal stem cells, like some RPS induced pluripotent stem cells or embryonic stem cells. People tried different types of stem cells, tried to regenerate the axon. It is possible for the cell body But for the axon, it's really hard, especially for the projection.

Implementation

We are planning liposomes to deliver our drugs. We will collaborate with local professors to produce the liposomes which will be encapsulating our peptides. We will also attach some ligands on the liposomes to ensure specific targeting. We have done research about the Schlemm canal. However, we will still be targeting trabecular meshwork cells as they are crucial for IOP regulation.

Implication

After this meeting with Prof. Chu, we have brainstormed our design of the liposome. In order to make sure our design is feasible, we decided to contact Prof. Dennis Ng from The Chinese University of Hong Kong.

Inspiration

Prof. Ng mentioned that liposomes are more expensive than cell penetrating peptides but it can bring hydrophobic or hydrophilic materials into the eye. Liposomes are also easier to control. Prof. Ng has suggested that microneedles is a very new technology. However, some will stick with the cells and translation is more difficult. Some molecules have intermolecular interaction. Cell penetrating peptide is a type of peptide which has this function such that cell penetrating peptides may form nanoparticles with water. Each drug requires different kinds of methods to enter the cell, eventually the first thing our members have to manage is to identify the structure of the drug.

Implementation

The interview with professor Ng has inspired our team about the liposome design. Our design employs a strategy of specific targeting to deliver our drugs, FT and BC to two cell types, trabecular meshwork cells and retinal ganglion cells respectively. Specific ligands will be conjugated with liposomes to target specific receptors on targeted cells, triggering endocytosis so our drug can enter the cells. For targeting TM cells, we will conjugate the liposomes with Wnt3a, CTGF, designed to engage their Frizzled and LRP5/6 receptors. Simultaneously, to promote RGC neuroprotection and minimize cell apoptosis, another part of liposomes will be conjugated with ligands for the TrkA receptor , which is mNGFB. Additionally, TAT will be presented in both liposome designs to increase the penetrating ability of liposomes and act as an assistant for endocytosis of our drug. This approach can significantly elevate bioavailability of our drug and therapeutic efficiency as off targeting issues will be prevented.

Implication

After this interview with Prof. Ng, we have been working on our liposome design, and we have kept on updating him with our latest liposome’s design through emails. We have affirmed our design through our discussion.

Inspiration

Currently, both high-tension glaucoma and normal-tension glaucoma are under the category of primary open angle glaucoma. Almost 70% of patients have primary open angle glaucoma.As our drug has the effect of lowering IOP, so the drug can also help normal-tension glaucoma patients. In the collaborative normal tension glaucoma study, even though the pressures were normal, when doctors gave pressure lowering drugs, it still helped and reduced the progression of disease by 30%. So Prof. Sharma thinks we could always justify that even though we’re targeting high pressure patients, but there are the normal-tension patients who are also getting helped by lowering pressure. Our drug would target the RGCs protection, which is happening no matter what race or pressure paradigm we have. The dosing of the drug can only be dependent upon how the lipid Nanoparticle and receptor is being attached, how many receptors are sensitized on the RGCs at that time, and how the lipid Nanoparticle would be endocytosed. The dosing can only be figured out how much of the lipid Nanoparticle is targeting the receptors, how it’s getting endocytosed and how much of the drug is then getting released. Prof. Sharma thinks we should focus more on the RGC side because trying to focus on two sides makes our project really ambitious. The trabecular mesh work part is already done by other scientists. It would be better for us to focus a lot of our energy on the RGC part because that’s the ultimate goal.

Implementation

After the interview, the optimal dosage for our drug has been brought into focus. We will include tests about drug dosage in the cell line experiments conducted in the collaboration with CUHK. Regarding our project's focus, we are committed to a dual-pathway approach, treating both elevated intraocular pressure (IOP) and retinal ganglion cell apoptosis as crucial mechanisms for preventing glaucoma progression. However, a major part of our project will be focusing on our product's unique ability to minimize RGC cell death. While current eye drops on the market focus on reducing IOP, there is a significant and growing market demand for RGC protective treatments that address the direct cause of vision loss in glaucoma. By directly targeting to minimize cell death, our solution targets the most critical factor in the formation of the disease, offering a pioneering and effective therapeutic strategy.

Implication

As this interview with Prof. Sharma reflects that our drug could benefit both high-tension glaucoma patients and normal-tension glaucoma patients, we hope to interview normal-tension glaucoma patients in order to understand their first-hand disabilities which may be different from high-tension glaucoma patients. After this interview, we wanted to find more experts in order to explore what we could improve in other aspects.

Inspiration

As for the carrier of the peptide, Professor Li stated that liposomes, though feasible for the project, are not new. For larger animal experiments or human use, it is less ideal. Instead, he suggested using pathogens as carriers or using needles to insert our drug into the eye. He pointed out that by using a pathogen as a carrier, it would provide us with a more effective way to apply the drug into the eye, as the nano carrier may not be able to pass through the various membranes of the eye. By using pathogens as a carrier, it can also synthesise the protein that we insert within the eye, leading to a more long-lasting effect. Professor Li recommended that the eye drop be used no more than once a day, or even once every two days or once a week. He noted that using the eye drop too frequently could lead to side effects, which may discourage patients from using it. Existing once-daily eye drops have set a standard, and therefore, a more complex design would require a longer duration of action per use.

Implementation

Our team has evaluated the approach of using engineered pathogens for ocular drug delivery. While this method offers a significant advantage in efficient protein synthesis, we are aware of the potential safety concerns it may raise.Therefore, our development strategy will prioritize safety, using liposomes as a delivery method. Regarding treatment duration, the goal is to minimize dosing frequency. We will engineer the formulation of drug components , targeting a once-a-day application.

Implication

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