Novel stem cell and gene therapy in diabetic retinopathy, age related macular degeneration, and retinitis pigmentosa

Major Points and Findings:

1. Introduction and Background:
   • Degenerative retinal diseases, such as diabetic retinopathy and macular degeneration, are leading causes of blindness in the developed world.
   • Current therapies can slow the progression of these diseases, but there’s potential for stem cell and gene therapy to reverse the effects of these conditions.
   • The therapies under investigation involve the use of stem cells for regenerating damaged retinal tissue, prolonged drug delivery, immunomodulation, and replacing mutant genes through viral vector delivery.
2. Degenerative Retinal Disease Prevalence:
   • Age-related macular degeneration is the primary cause of blindness in Caucasians over 40 years in the USA.
   • Diabetic retinopathy is the leading cause of vision loss for those aged 20 to 74.
   • Retinitis pigmentosa affects 1 in 3000–7000 people, making it a common inherited retinal disease leading to blindness.
3. Current Treatments:
   • FDA-approved treatments for neovascular age-related macular degeneration and complications from diabetic retinopathy involve frequent anti-vascular endothelial growth factor (VEGF) intravitreal injections.
   • Diabetic retinopathy is also treated with anti-VEGFs and laser photocoagulation.
   • For retinitis pigmentosa, treatments have been about reducing further damage. However, the FDA has approved a gene therapy called Luxturna, which targets RPE65.
4. Stem Cells in Retinal Therapy:
   • Stem cells are identified as cells that are self-renewing and can differentiate into multiple cell types.
   • There are retinal stem cells localized to the pigmented ciliary margin capable of differentiating into various retinal cells.
   • Types of stem cells include human embryonic stem cells (hESCs), bone marrow stromal cells (BMSCs), human mesenchymal stem cells (hMSCs), human pluripotent stem cells (hPSCs), and human retinal progenitor cells (hRPCs).
5. Potential of Stem Cells:
   • The transplantation or activation of stem cells has potential in regenerating damaged retinas.
   • Some studies have shown that transplanted stem cells can integrate into the retina, form functional synapses, and improve vision in mouse models of degenerative retinal disease.
   • Stem cells can also play roles as vehicles for drug delivery, immunomodulatory agents, and mediators of tissue regeneration.
6. Challenges and Observations:
   • One of the barriers to stem cell transplantation therapy is inducing the incorporation of transplanted cells into the host cell structure, potentially complicated by immune reactions.
   • Some studies have shown that stem cells can migrate to the retina and differentiate into various cells, but few have expressed photoreceptor markers.