PROJECT DESCRIPTION

Preserving Retinal Cells Survival and Function for Potential Clinical Studies in T1D

One of the major complications in type 1 diabetes (T1D) is vision impairment. Diabetic retinopathy is the leading cause of blindness among working-age adults, and accounts for a high degree of disability and long-term morbidity. Current approaches to treat diabetic retinopathy have limited success to restore vision when the retina is damaged. We are investigating the feasibility and technical challenges associated with the far-reaching concept of retinal cell replacement, a future goal that we believe has the potential to improve vision to blind T1D’s.

We envision a retinal cell replacement program consisting of several stages with multi-disciplinary and multi-institutional clinicians and scientists. For this project, we want to address 2 phases: Phase 1 consists of maintaining the viability of retinal tissue in postmortem eyes. Phase 2 consists of identifying conditions that allow cells to integrate into the retina.

Over the past three years, we have generated preliminary data that supports the feasibility of Phase 1. With a multidisciplinary team consisting of representatives from regional eye banks, organ donor programs, visual chemists, electrophysiologists and clinicians, we have succeeded in developing the techniques for maintaining or reviving the viability of macular and peripheral retinal tissue in postmortem human eyes. Initially, we found the neuronal viability in the human macula from donor eyes was compromised. We attributed the poor outcomes to multiple obstacles, including prolonged death-enucleation times. To solve these problems, we adopted a novel approach, using human organ donor eyes.

Dr. Hanneken became a registered organ donor research recipient and established a collaboration with LifeSharing, a major organ donor Society in San Diego and Imperial Valley. She harvested human organ donor eyes at the time that the transplant team was procuring heart and lung tissues, which overcame multiple obstacles. The responses with human organ donor eye tissues were significantly better, particularly in the outer retina where photoreceptor responses could be measured with good electrical amplitudes. However, there are still challenges and technical factors that reduce viability, particularly in the inner retina function.

In this project, we will use sophisticated approaches to examine the timing and the harvesting conditions of the human eye donor to optimize neuronal survival and/or revival of retinal neurons. These results are expected to establish criteria and protocols for potential retinal cell replacement capable of generating and transmitting light-evoked signals from photoreceptors all the way to the retinal ganglion cells, which are the output neurons of the retina.