This story is part of a series on the current progression in Regenerative Medicine. This piece is part of a series dedicated to the eye and improvements in restoring vision. This piece also marks part one in a small series on diabetic retinopathy.


In 1999, I defined regenerative medicine as the collection of interventions that restore to normal function tissues and organs that have been damaged by disease, injured by trauma, or worn by time. I include a full spectrum of chemical, gene, and protein-based medicines, cell-based therapies, and biomechanical interventions that achieve that goal.


Diabetic retinopathy, a condition that develops in people with diabetes, is a silent thief that robs them of their vision. It is one of the leading causes of blindness in the working population worldwide, and its prevalence is steadily rising. In 2021, diabetic retinopathy affected an estimated 9.6 million people in the US, comprising 26.43% of those with diabetes.


With such alarming statistics, it is critical to understand the current treatment options available to these individuals. From innovative drug therapies to clinical trials and gene therapy, the field of ophthalmology has made significant strides in the past few years in treating this debilitating disease. 


What is Diabetic Retinopathy?


Diabetic retinopathy is a diabetes-related complication that impacts the blood vessels in the retina. The retina, located at the back of the eye, is responsible for visual perception. High blood sugar levels can cause damage to the blood vessels in the retina, leading to a range of symptoms and complications. The disease can progress through two main stages: non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR), with the latter being the more severe.


Several factors can elevate the risk of developing diabetic retinopathy. These include uncontrolled blood sugar levels, high blood pressure, high cholesterol, obesity, pregnancy, and smoking. As the duration of diabetes increases, the likelihood of diabetic retinopathy also rises. Timely identification and intervention are critical in mitigating vision impairment and reducing the complexities associated with this ailment.


Several pathways and mechanisms are identified that play a significant role in the development and progression of diabetic retinopathy. A study by the University of Malaya outlines these pathways and mechanisms. One of the critical pathways is the polyol pathway, which converts excess glucose to sorbitol and fructose. This process leads to osmotic stress and oxidative damage in the retina. 


Another important pathway is the protein kinase C (PKC) pathway, which produces vascular endothelial growth factor (VEGF), leading to abnormal retina growth. In addition, non-enzymatic glycation, inflammation, oxidative stress, and activation of the renin-angiotensin system (RAS) are also implicated in the development of diabetic retinopathy. Failure to address these pathways and mechanisms can result in retinal damage and vision impairment if left unattended.


Current Treatments for Diabetic Retinopathy


Effectively managing this condition requires maintaining tight control over blood glucose and blood pressure levels. This is typically the first course of action that most doctors recommend to prevent or slow down the progression of the disease. Early detection can help slow its passage in the initial stages by closely monitoring your blood glucose and blood pressure. 


Laser treatment is frequently used in later stages to stop further damage and prevent vision loss. It targets and halts the growth of new, fragile blood vessels that can bleed within the eye. The procedure involves multiple treatments that may be necessary to ensure the best outcome, and the frequency of treatment depends on the severity of the condition. It is a safe and effective outpatient procedure that does not require hospitalization. However, laser treatments are limited in their ability to restore vision that has already been lost and may cause some degree of vision loss following the procedure due to the destruction of healthy tissue in the treated area.


When laser treatment fails, or in cases of advanced retinopathy, anti-VEGF medication is a viable treatment option. These medications are directly injected into the gel-like substance in the eye called vitreous, which helps to prevent the growth of new blood vessels and reduce fluid buildup. Anti-VEGF medication works by blocking the action of VEGF protein, which stimulates the development of new blood vessels in the retina. As a result, anti-VEGF medication can prevent abnormal blood vessel growth in the retina. Anti-VEGF treatment for diabetic retinopathy requires frequent and costly injections, leading to issues with compliance and accessibility for some patients.


Another option is steroids. Steroid implants can be placed in the eye to reduce inflammation and swelling that can cause vision loss in patients with diabetic retinopathy, particularly those with macular edema. In cases where laser treatments are not an option due to the severity of the retinopathy, eye surgery may be performed to remove blood clots or scar tissue accumulated in the eye due to retinopathy. This procedure can help restore vision in less severe cases of diabetic retinopathy. It’s essential to mention that while steroid implants may be useful for treating diabetic retinopathy, they come with certain limitations. They can cause an increase in intraocular pressure, lead to cataract formation, and other complications that require careful monitoring and management by a qualified healthcare professional.


Cutting-Edge Treatment Options


In addition to the standard treatments currently available for diabetic retinopathy, researchers are exploring new and innovative methods to combat this eye disease. One such cutting-edge treatment is gene therapy, which involves the insertion of healthy genes into the retina to replace faulty ones responsible for developing diabetic retinopathy. Although gene therapy is still experimental, it has shown promising results in treating and managing this condition.


Another potential treatment option being explored by researchers is stem cell therapy. It involves replacing damaged or dead cells in the retina with stem cells. However, there are certain challenges that limit its effectiveness, such as the risk of immune rejection of the transplanted cells, difficulties in selecting the appropriate type of stem cells, and the potential for tumor growth. Although still in the early stages of development, stem cell therapy holds great promise as a future treatment option for individuals with diabetic retinopathy.


Researchers are also investigating using a protein called NOX4 as a potential therapeutic target for diabetic retinopathy. NOX4 is recognized for its involvement in the development of this disease. By targeting this protein, researchers hope to develop new treatments to manage and treat diabetic retinopathy effectively.


Overall, the ongoing research into new treatments for diabetic retinopathy offers hope for individuals living with this condition and may lead to more effective treatments and improved outcomes in the future.


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