Age-Related Macular Degeneration: The Regenerative Treatment Approach

Age-related macular degeneration is a prominent cause of blindness in older people. It results in irreversible loss of vision and developing reliance on others for daily activities. However, the current treatment can reverse the loss of vision or cells but can only slow the progression of the disease. The complexity of the disorder requires a regenerative treatment. Stem cells, an integral part of regenerative medicine, can effectively slow the disease and also restore the retinal damage.

Age-Related Macular degeneration

The retina is a transparent layer of the eye responsible for vision. Its central region is termed the macula, a multilayered area that maintains basic functions and detailed parts of vision such as reading, face recognition, writing, etc. Its different layers contain a network of blood capillaries, epithelial membranes, and photoreceptor cells that impart sharpness and color to the visual image. Age-related macular degeneration (AMD) results from the damage of cells in the macula region. It leads to loss of central vision while not affecting peripheral vision.

Types of Age-Related Macular Degeneration

AMD can be classified further, depending on the underlying cause:

Dry AMD: Dry, also known as non-neovascular or atrophic AMD, constitutes up to 85% of AMD cases but has more favorable outcomes with regard to visual loss. It occurs due to the damage of epithelial membrane cells in the macula. The causes include oxidative stress and accumulation of protein deposits. These deposits or drusen increase in size and quantity with the increasing stage of the disorder. At the advanced stage, the retinal epithelial cells and photoreceptor cells begin to die, forming scars or lesions in the eye. Photoreceptor cells convert the visual input into a nerve signal and transmit it to the brain. Therefore, the loss of these cells significantly impacts the visual capacity.  In a few cases, the advanced stage of dry AMD can proceed to cause wet subtype.

Wet AMD: Wet or neovascular or exudative AMD accounts for only 10-15% of cases but is responsible for vision loss in 90% of wet AMD patients. It begins with insult or injury to the vessels in the macular region that stimulate repair mechanisms. These mechanisms include inflammation and angiogenesis. The injury releases vascular endothelial growth factor (VEGF) for vessel formation or repair (angiogenesis). However, expression of abnormal types of VEGF can form aberrant vessels. The growing vessels cause blood leakage into the retina.

Symptoms of Age-Related Macular Degeneration

Dry AMD can be detected by retinal deposits or drusen. Wet AMD progresses more rapidly, with worsening vision, severe distortion, or even blind spots due to fluid accumulation caused by vessel rupture. The risk factors for AMD include social factors (age, gender, race), cardiovascular disorders (hypertension), lifestyle (smoking, diet), inflammatory, genetic, and hormonal.

Early-stage disorder might not show any symptoms. But gradually, patients might experience blurring and distortion in vision with diminishing contrast as the disorder progresses. It is particularly difficult to read or write in fine print. Slowly, the central vision deteriorates. One might find it difficult to see in low light conditions, or the straight lines might appear wavy.

Current Treatment

The treatment options vary on the subtypes of AMD. Wet AMD is treated by anti-VEGF therapies. These therapies focus on the abnormal expression of VEGF subtypes that form inadequate blood vessels susceptible to leakage. However, dry macular degeneration does not respond to these therapies. Treatments like pegcetacoplan and avacincaptad pegol are still in the developmental phase. Dry AMD therapy usually focuses on dietary supplements to slow the visual loss. Additionally, tools for visual aids, such as a magnifier, adjusting the level of light, increasing the font size, etc., are recommended. However, none of the therapies can cure the damage and only focus on delaying the visual loss.

How do stem cells improve Age-Related Macular Degeneration?

Stem cells, with their regenerative potential, have brought a different approach to AMD treatment. Mesenchymal stem cells (MSCs) have various characteristics that have therapeutic effects and can reduce the disorder progression and visual loss in the following manner:

• MSCs can differentiate into retinal cells, such as retinal epithelium and photoreceptor cells.
• They secrete protective factors, such as BDNF, NGF, CNTF, HGF, etc., that protect retinal nerve cells from damage.
• MSCs release anti-inflammatory molecules that reduce inflammatory stress on cells and also incline immune response towards repair.
• MSCs consume reactive oxygen species by the Nrf2 signaling pathway.
• They also tightly balance the blood vessel formation by releasing both anti-angiogenic and pro-angiogenic growth factors, restoring the integrity of blood vessels and reducing leakage.

The implantation of MSCs in the eyes has demonstrated improvements in visual function without causing any adverse complications. However, the treatment requires standardization and phase III clinical trials for clinical translation.

Conclusion

Stem cells are redefining the treatment approach to degenerative disorders by repairing the damage. AMD causes blindness in older people, resulting in increased dependency on others. The intricacy of the disorder mandates a holistic level therapy. Mesenchymal stem cells with their diverse properties can act on different aspects of the disorder. Their administration have not only delayed visual loss but also improved visual function, exhibiting the repair capacity of MSCs. The regenerative approach of MSCs can provide the much wanted cure of AMD. Advancells is contributing to this approach for macular degeneration treatment in India by delivering premium quality stem cells after rigorous testing.