Overview

In this project, our Human Practices (HP) work focused on the social needs surrounding age-related cataracts. Through literature review, questionnaire surveys and field visits, we identified the lack of early intervention methods and insufficient patient awareness as key pain points. Consequently, we selected superoxide dismutase (SOD) as the intervention approach, which aligns with scientific principles while meeting users' demand for effective medication. Through in-depth analysis of both early-stage and post-operative patients, we identified an urgent need for effective interventions among early-stage individuals. Guided by expert recommendations, we refined the project, establishing preliminary product formulations and development roadmaps—including clinical trial protocols, partnership models, and pricing strategies. Ultimately, we are committed to developing an SOD-based eye drop product specifically targeting “early-stage patients aged 50+.”

Stakeholders	Key Findings/Suggestions	Our Actions&Impact
The Public(Online questionnaire&Offline visit）	Cognition: High awareness of diseases, but limited understanding. Needs: High interest/acceptance in the pharmacological approach. Product concerns: Efficacy, safety, affordability.	1. Conduct offline visits to enhance the depth of science popularization; 2.Carry out inter-generational science popularization to improve the effectiveness of science popularization; 3.Plan product specifications and pricing; 4.Pay attention to communication methods and emphasize that SOD-eyedrop is far from a traditional drug.
Early-stage Cataract Patients	Few daily eye - care measures Unaware of the “antioxidant” effect High demand	1.Strengthen the verification of drug safety 2.Optimize the market promotion strategy: ··Enhance public trust through academic cooperation. ··Combine promotion with science popularization to raise public awareness of eye - care.
Post-surgical patients	Trust in surgery Resist new products, and prefer traditional verified drugs
Optic Nerve Learner	Pointed out the difficulties of SOD eye - drops: ··Corneal penetration, aqueous humor stability, lens targeting; ··Adjusting pH and osmotic pressure to match that of tear fluid can reduce eye irritation.	Encapsulate SOD with nanoparticles/liposomes; Adjust pH to 6.8-7.4 and osmotic pressure to 260-320mOsm/kg; Build a model to simulate the “efficacy-time” relationship to verify the feasibility of SOD eye-drops.
Ophthalmologists	SOD delivery, stability, and cost issues need to be addressed.
Pharmaceutical Expert	“Golden time” for cataract prevention Formula suggestions Industrialization suggestions	Identify the target users as people aged 50 and above; Replace toxic preservatives with Oxyd®; Plan a 5-7 - year clinical trial and consider cooperation with CDMO to reduce risks.
Mathematical statistics Expert（Pharmacokinetics）	Suggested building mathematical models to verify efficacy	Constructed models to simulate the diffusion efficiency of SOD-drug delivery

1. Social Needs and Technological Compatibility

1.1 Why Did We Focus on Age-Related Cataract?

With the acceleration of population aging, age-related cataract has become the leading cause of blindness and visual impairment worldwide. It is estimated that age-related cataracts account for about 51% of global blindness cases and represent a significant proportion of visual disability in developing countries [1].

In China, the prevalence increases sharply with age: approximately 7.9% among individuals aged 50–59, 24.9% among those 60–69, 51.7% in the 70–79 age group, and up to 78.4% in people over 80 [1].

At present, cataract treatment relies primarily on surgery, which is usually performed at middle or late stages. There are no widely effective pharmaceutical or early intervention strategies available [2] [3]. Moreover，many elderly patients have limited understanding of “early intervention,” often relying only on reduced screen use or conventional eye drops, while being unaware of scientific antioxidant-based strategies [2].

This gap in awareness and therapeutic options means that them often miss the best intervention period, which worsens quality of life.Against the backdrop of elderly’s desire for social identity and better life, preventive products fit their needs: avoiding surgery, staying functional and independent, which boosts self-esteem and the sense of controlling their health.

1.2 Why Did We Chose SOD (Superoxide Dismutase)?

Superoxide dismutase (SOD) is a key antioxidant enzyme that catalyzes the dismutation of superoxide anions, alleviates oxidative stress, and protects lens tissue from damage [4][5].Evidence suggests that SOD1 levels in the lens are negatively correlated with cataract progression. Reduced SOD activity accelerates cataract formation, while regulated SOD gene expression affects enzyme activity and lens health [6].Moreover, experimental formulations such as SOD-containing gels have demonstrated potential in delaying posterior subcapsular cataracts [4].

Among the 61 elderly people over 50 years old who participated in our questionnaire interview, 51% preferred pharmaceutical intervention as a treatment option and emphasized their expectation of its "effectiveness". This finding suggests that an effective, non-surgical option would meet a strong, unmet demand. SOD, with its antioxidant properties, aligns well with this expectation and shows strong potential for future development and application.

In addition, through market research, we found that eye preparations are mainly in liquid form, and the main product types are eyewashes and eye drops. Considering the preservation and potency of enzyme preparations, we chose eye drops as the product form after comprehensive consideration. Moreover, eye drops, with their small - sized packaging, are convenient for users to use and carry. Based on this choice of product form, we continued with the following research.

2. Preliminary Evaluation

2.1 Online Questionnaire

We designed a questionnaire to collect data on the public’s awareness of cataracts, their demand for and acceptance of preventive products.Below are the survey results and a detailed analysis.

2.1.1 Public Knowledge

Key Findings：

Low Detailed Knowledge：While over half (52.29%) of all the participants have heard about cataracts, only 14.38% are aware of treatments and symptoms. This suggests there is a massive gap in detailed public knowledge, even if so more likely among the older age group.

High Perceived Prevalence：The majority (53.59%) have someone with cataracts, indicating that the condition is widespread across social networks and will influence perceived risk and receptiveness to accept interventions.

Our Actions

​ ● Offline Community Engagement: In order to directly reach out to the elderly and conduct promotional education among them, we visited some communities offline and had face-to-face conversations with the elderly in these communities. Through this activity, not only did we successfully carry out promotional work in the sense of "education", but more importantly, we clearly and intuitively felt the importance and necessity for science to step out of the "laboratory" and penetrate into the masses.

​ ● Communication: During our conversations and daily promotions, we pay attention to the way of communication. We position the eye drop not merely as a drug, but as a lively instrument for life, freedom, and the pursuit of leisure or life interests (such as reading, being with grandchildren, participating in community activities). This meets the needs of social identity and significance for the elderly.

​ ● Intergenerational Knowledge Transfer: We hope to use the younger generation as a bridge to convey common sense of eye protection and the advantages of preventive products to the elderly. Therefore, we designed online live - streaming promotions, offline courses for children, and promotional activities in high schools. By raising the awareness of young people and children, we aim to indirectly influence the elderly. At the same time, we hope that the younger groups, starting from this, will show more care to the elderly around them.

2.1.2 Early-Stage Intervention Preferences & Acceptance of Drugs/Supplements

Key Findings：High Interest/Acceptance in Pharmacological Approach

Almost half (47.06%) of the total participants were interested in medication intervention (e.g., antioxidant eye drops) for early/mid-stage cataract therapy, followed by lifestyle (38.56%) and dietary (14.38%) interventions（Figure a）. At the same time, we separately analyzed the choices of the interviewees aged over 50 among these three intervention methods, which were 29.51%（lifestyle）, 19.67%（dietary）, and 50.82%（medication） respectively.（Figure b）This reflects a very potential degree of acceptance of a preventive eye drop product among the target age group.

2.1.3 Needs & Expectations of the Target Group for Eye Drops

Key Findings：

Side effects (79.74%), safety of the ingredients (71.9%), and ineffectiveness (56.86%) are the leading concerns when buying eye drops. Effectiveness (95.42%) and safety (81.05%) far outweigh the others as the most important considerations for a preventive cataract drop.

Recommended sizes (5mL-10mL/bottle, 50%) are preferred, and presumably a compromise between convenience and cost. The most acceptable price is under 100 yuan/10mL (43.14%), followed by under 50yuan/10mL (33.66%).

Our Actions：

We understand people's concerns, and in fact, people's concerns about synthetic biology products and SOD-containing eye drops stem from a lack of understanding of unknown technologies, and on the other hand, it also makes us aware of the importance of proof of safety of preventive drugs. Therefore, we have made awareness and education and drug safety validation our next priority.

In addition, in our business plan, after comprehensively considering issues such as cost, portability of use, and drug preservation, we plan to design the packaging as 10 ml per bottle, with a price of 79 yuan per bottle. The 10 - ml packaging is sufficient for one - month daily eye-care use. If the product is covered by medical insurance, the price will be even lower.

2.2 Offline Community Visits

Aligned with our HP strategy and project (investigating oxidative stress in age-related cataracts), our team did a summer outreach for seniors across several cities,such as Hangzhou,Tianjin.

We gave custom hand fans—relieving heat while sharing simple cataract/oxidative stress info—and had recipients fill out a survey to grasp their related knowledge, misconceptions and concerns. This non-intrusive approach (better than our online survey for reaching seniors) gathered data, raised awareness and turned heat into an engagement chance, in line with iGEM’s responsible science spirit.

​ Our fan had concise information on cataracts (definition, symptoms, free radicals’ role), our team name (Nanjing-BioX), and a Douyin QR code. We approached seniors in parks/squares/residential areas during peak hours, offered the fan to beat heat, explained we were students doing eye health research, and politely invited them to scan the code and fill a survey—stressing it was optional (fan as gift either way) and offering help with scanning/reading.

Outcomes & Impact

A significant majority of respondents were aware of cataracts but had little to no knowledge of oxidative stress as a contributing factor. This validated our need for public education. Beyond the survey data, our face-to-face conversations yielded unexpected insights: the overwhelming consensus that "everyone knows someone with cataracts" confirmed the high prevalence and social relevance of the disease we are addressing. This recurring statement transformed our project from an abstract scientific concept into a tangible response to a widely recognized community health issue. When discussing potential treatments, respondents immediately raised questions about "the safety of new eye drops" and, crucially, "cost and medical insurance reimbursement." Their focus was not just on the existence of a treatment, but on its practical affordability and safety, reminding us of the economic dimensions of health that we must consider. This shifted our HP focus towards the economic and psychological barriers to care. The elderly respondents expressed high trust in information provided by students, which strengthened our commitment to being accurate and responsible communicators.

Integration & Reflection

A fascinating question we received was: "Why are you, as young scientists, asking for our opinions?" This provided us with a perfect opportunity to explain that responsible science does not happen in a vacuum; it must "step out of the lab" to understand the needs, concerns, and social context of the community it aims to serve. The feedback on cost and safety shifted our focus from merely proving a scientific concept ("can we do this?") to evaluating its practical implementation ("how would this be used?"). It forced us to consider the economic viability and public trust necessary for any potential product to have real-world impact. The question about why we consult the public reminded us that we act not just as researchers, but as communicators and listeners. Our answer—that science is a dialogue with society—is now a cornerstone in our project identity and all our subsequent public communications. This activity was not a standalone event but a core component of our Human Practices cycle. The data collected directly integrated into our project design. Understanding the public's concern of both surgery and new therepeutics reinforced our motivation to explore safer and more guaranteed strategies for developing an SOD-based eyedrop. We tailored our future content, such as releasing a series of lectures on the elementary of synthetic biology, to address this specific gap. This activity will serve as a foundation for our future HP efforts: We plan to create content that addresses the specific concerns raised and expand our outreach of increasing the availability of educational materials.

By meeting the community where they were—literally and figuratively—we ensured that our iGEM project remains grounded in empathy, responsibility, and a genuine desire to serve.

3. Patients' Pain Points and Demands

We hoped to understand the demand for products among patients at different stages and their expectations of new products through direct communication with them. We recruited two patients in the early stage of the disease who did not meet the surgical indications and two patients who had already undergone surgery. To protect the privacy of patients and out of respect for their wishes, we will not disclose information such as photos taken during our conversations with them.

3.1 Conversation with Early-stage Cataract Patients

Patients Information:

One patient is 76 years old and the other is 72 years old. Both are retired and have good living and eye - using habits. They either don't use or only occasionally use electronic products.

The onset time and aggravation of cataract - related symptoms (such as blurred vision, color vision changes, photophobia, etc.) vary between the two elderly people.

One patient has had symptoms for many years, but according to the annual physical examination results, there has been no significant aggravation. The other patient gradually felt blurred vision as they aged, and was then diagnosed with mild cataract during a physical examination.

Early-stage cataract patients are the group we focus on the most. We got in touch with two patients who were willing to be interviewed, and learned from them about the living conditions of early-stage patients and their acceptance of preventive eye drops.

Both elderly patients said that they had few daily eye - care measures and seldom used eye drops, because they thought these measures had "little effect" in delaying vision loss and improving lens turbidity. They didn't know much about the role of "antioxidation" in cataract prevention, and their understanding of early - stage protection was limited to "reducing eye use" and "using eye drops". However, both expressed their willingness to learn more about this if possible.

Regarding the demand for and expectations of new eye drops, they showed great interest. The aspects they cared about most, in order, were reducing the probability of future surgery, delaying the surgery time, and slowing down the rate of vision loss. They hoped that the new drug could reduce the impact of cataract on scenarios such as using electronic devices, outdoor activities, and driving, thus improving the convenience of life.

3.2 Conversation with Patients Who Have Completed Cataract Surgery

Patients Information:

Both are cataract patients who have undergone surgery.

Both patients are around 75 years old. One of them had a relatively severe condition, and their vision was almost non - existent before the surgery.

In order to understand whether post - operative patients have a need for eye drops that prevent recurrence, we interviewed relevant patients. We found that they had a high level of trust in surgery, but instead showed resistance to eye drops, believing that long - term use of drug protection would incur additional time and cost. At the same time, they had a relatively strong negative attitude towards new products in synthetic biology and were more inclined to choose traditional drugs that have been clinically verified over the long - term and whose safety and effectiveness have been recognized.

Through this conversation, we realized that perhaps due to educational and habitual factors, some elderly people in China lack trust and interest in new things and are unaware of the importance of long - term eye health maintenance. This has further motivated us to work hard to verify the safety of the drug and strengthen the promotion of new products. Therefore, in our business plan, we have also optimized our marketing promotion strategy.

4. Technical Guidance and Project Optimization

4.1 Suggestions on scientific basis and breakthroughs in technical difficulties

Mr.Zheng is a graduate student in optic nerve-related majors.

Mr. Zheng stated that currently, there are no reliable clinical studies proving that exogenous SOD administered via eye drops can penetrate the human eye and delay cataracts. He also pointed out technical difficulties such as "corneal penetration, aqueous humor stability, and lens targeting". Regarding these issues, he proposed theoretical solutions, such as encapsulation with nanoparticles/liposomes, using thermosensitive gels to prolong residence time, applying penetration enhancers, adopting PHMB preservatives or using preservative - free sterile single - dose packaging. The pH should be maintained at 6.8 - 7.4, and the osmotic pressure at 260 - 320 mOsm/kg to approximate the tear fluid environment. Additionally, protein protectants like glycerol, glycine, and mannitol can be added.

4.2 Current Clinical treatments and product risk warnings

To gain a deeper understanding of the clinical challenges in developing enzyme - based eye drops for preventing or slowing down cataract formation, our team also interviewed Dr. Ren, an ophthalmologist.

Dr. Yanhan Ren is a senior resident at the University of Massachusetts, specializing in ophthalmology.

How to transfer superoxide dismutase (SOD) in eye drops to the cataract site? Enzyme-based eye drop treatments may be unstable and ineffective. How to solve this problem? Moreover, synthesizing SOD-based eye drops and preserving them to maintain the enzyme's biological activity is costly, which may hinder the large-scale production of such eye drops.

Dr. Ren believes that these three reasons may be the challenges we must address before using SOD - enzyme-based eye drops for medical purposes.

We carefully considered the recommendations of Dr. Ren, and accordingly revised and supplemented the experimental design, particularly regarding the composition of the eye drops and their clinical translation.

From our interview with Dr. Ren, we know that selecting a highly stable form of SOD is central to delaying cataract progression. In the product development and clinical translation stages, two key challenges are “drug penetration” and “targeted delivery.” SOD must rely on carrier technologies—such as nanoparticles, liposomes, and extracellular vesicles—to overcome physiological barriers in the eye, including the cornea, aqueous humor, and lens.

Therefore, based on literature review and ongoing research, our project plans to encapsulate SOD using nanoparticles or liposomes to enhance its stability and penetration. Additionally, we intend to use a thermosensitive gel to prolong the drug’s retention time on the ocular surface, thereby increasing its contact with the cornea and aqueous humor.

Regarding delivery vehicles, we have also noted the significant potential of extracellular vesicles for targeted ocular delivery. Previous studies have demonstrated their therapeutic efficacy in treating neurogenic retinitis, and we plan to explore this technology in future stages of our research.

Based on our interview with Dr. Ren, we have also formulated a preliminary eye drop synthesis plan.

• Penetration Enhancers: Agents such as hyaluronic acid and bile salts are added to the eye drop to improve SOD’s ability to penetrate ocular barriers.

• Physiological Compatibility: The pH of the eye drop was adjusted to 6.8–7.4 to better match the natural pH of tears; Osmolarity was adjusted to 260–320 mOsm/kg to align with tear osmolarity and reduce ocular irritation.

• Protein Stabilizers: Glycerol, glycine, and mannitol were incorporated as protein protectants to prevent SOD degradation during storage and within the physiological environment.

• Preservative-Free Packaging: Sterile, single-dose packaging were used without preservatives to avoid corneal toxicity associated with agents like benzalkonium chloride.

4.3 Productization path and formulation suggestions

To understand how our project could move from the lab to real-world use, we interviewed Prof. Shu, a pharmaceutical expert with experience in drug development and commercialization.

He emphasized the “golden intervention time” for cataract prevention: supplementing SOD before irreversible lens protein aggregation occurs. This confirmed that our focus on early-stage prevention is clinically meaningful.

On formulation, Prof. Shu suggested replacing toxic preservatives with Oxyd®, and outlined the key features our engineered SOD should meet: high stability under sterilization, resistance to enzymatic degradation in tears, and small molecular size for better corneal penetration. These insights directly shaped our proposed eye drop composition.He also highlighted the long path of drug productization: 5–7 years of clinical trials, strict GMP compliance, and potential use of CDMO outsourcing or licensing to reduce early-stage risks.

This interview was highly valuable for us: it connected our experimental focus with industry standards, guided the design of our formulation, and informed the timeline and strategy in our Entrepreneurship Plan.

4.4 Simulating Mn-SOD Eyedrop Efficacy based on Multi-Scale math model

Due to the limitations of safety regulations, we were unable to do specific drug efficacy verification, so we sought help from Mr.Deng, graduated from Fudan University with a master's degree in mathematics and statistics, hoping to use the knowledge of mathematical modeling to simulate predictions.

Initially, we planned to build only a 0D homogeneous model to quickly assess the pharmacoviability of Mn-SOD, but it reduced the eyeball to a "dot" that did not reflect the real challenges of drug delivery and could not answer the core questions of "how much drug will reach the lens" and "how long it will take". Mr.Deng suggested that we adjust the efficacy evaluation of Mn-SOD from a 0D homogeneous model to a 1D spatial model. We can capture the natural attenuation of drug concentration from the corneal surface to the lens surface, which is an important prerequisite for predicting the actual dose of the target.

Finally, under the guidance of Mr. Deng, we constructed a set of multi-scale mathematical models to quantitatively simulate the "efficacy-time" relationship between Mn-SOD eye drops in the eyeball and further verify the feasibility of eye drops with Mn-SOD as the core ingredient for early prevention of cataracts.

Our mathematical models employ a bottom-up, simplified to complex modeling strategy. Firstly, at the molecular biological mechanism (microscopic) level, the catalytic reaction mechanism of Mn-SOD catalytic scavenging of ROS was characterized, and the enzymatic reaction rate equation was derived based on this. On this basis, at the macroscopic 0D system level, the ocular environment is simplified into a homogeneous "reaction chamber", and ordinary differential equations (ODEs) are established to simulate the dynamic process of drug and ROS concentrations with time. Further, at the macroscopic 1D spatial expansion level, reaction-diffusion partial differential equations (PDEs) are introduced to simulate the spatial distribution gradient of drugs and ROS in the eye, so as to achieve higher fidelity prediction of the spatiotemporal evolution of drug efficacy.

The predicted results significantly improve the efficiency and accuracy of formulation screening and dosing regimen design, and strengthen our confidence.

5. Product Implementation & Future Plan

Based on the survey of the elderly population and Professor Shu's suggestions, we targeted the target group as those aged 55 and above, with limited access to medical resources and a desire for social identity. To promote the implementation of SOD-based eye drop products, we plan to start from the following aspects:

In product development, the formula is optimized according to expert opinions, SOD is encapsulated with nanoparticles or liposomes to improve stability and permeability, pH and osmotic pressure are adjusted, and sterile single-dose packaging without preservatives is adopted. Clinical trials are planned for 5-7 years, and GMP standards are strictly followed.

In terms of production cooperation, consider cooperating with CDMOs for large-scale production, and cooperate with academic institutions and medical institutions to improve product quality and accessibility with the help of resources from all parties.

At the marketing level, carry out a wide range of popular science education activities, and popularize the knowledge of early cataract prevention and the advantages of products to the target population through online platforms, offline lectures and other forms. For people aged 55 and above, formulate precision marketing strategies, and use community publicity, common media for the elderly and other channels to promote. Establish a patient support system, provide product usage guidance, regular return visits and other services to enhance patients' trust in products. Actively communicate with the medical insurance department to strive to include the product in the medical insurance catalogue, reduce the cost of medication for patients, and improve the market acceptance of the product.

In the future, we will systematically evaluate Mn-SOD’s enzymatic performance under varied thermal conditions, establish a temperature-activity-stability relationship, integrate data into mathematical models to optimize formulation design and efficacy prediction; meanwhile, we will develop advanced targeted delivery strategies for Mn-SOD eye drops and validate them via in vitro, ex vivo and in vivo experiments to overcome ocular physiological barriers and enhance bioavailability and therapeutic efficacy.

Reference

[1]Bromgollows et al. Age-related cataracts account for approximately 51% of global blindness, with prevalence in China rising sharply with age. Global Reports on Cataract and Blindness.

[2]Wang et al. Advances in antioxidants and protein aggregation inhibitors for the prevention and treatment of cataract, noting that current interventions still rely primarily on surgery. Spandidos Publications, 2024.

[3]Medscape. Cataract management remains dominated by surgery; early diagnosis and intervention are limited. emedicine.medscape.com.

[4]Lee H, Park SJ, Kim JH. Oxidative stress and antioxidants in cataract development. Exp Eye Res. 2023;226:109517.

[5]Antioxidants (MDPI). SOD catalyzes the dismutation of superoxide anions, serving as a major regulator of oxidative stress. Antioxidants. 2023.

[6]Nature & Sci Rep. SOD1 is the primary antioxidant defense in the lens; decreased expression is associated with cataract, while overexpression protects against oxidative damage. Sci Rep. 2016;6:34704.