High-Resolution In Vivo Imaging for Early Detection and Treatment of Retinal Degeneration

Principal Investigator

University of California, Davis
Davis, CA
Acknowledgement
This grant is made possible in part by a grant from the Ivan Bowen Family Foundation.

Summary

Blindness is commonly caused by the death and disappearance of light-sensing cells in the retina. One big-picture goal of our research is to identify cells in distress and to heal them before they die and before patients lose their sight. Because doctors have the ability to look inside the eye as part of routine exams, our research is developing new ways to image cells in the living eye, providing a new “window to health,” with the ultimate goal to delay or prevent blindness through early detection.

Detailed Non-Technical Summary

The first part of vision begins in the photoreceptors of the retina, which transduce photons of light into electrical signals. Our lab examines the biochemical and biophysical properties of signaling in photoreceptors, as well as the consequences of defective signaling on visual performance.

We are also trying to understand why and how photoreceptors die, which is the leading cause of blindness in humans.  Photoreceptor degeneration, like all neurodegenerative diseases, leads to microglial activation and neuroinflammation.  We are investigating the regulation of neuroinflammation, its relationship to neovascularization, and its helpful vs harmful consequences for preserving neuronal and synaptic function.

A common early indication of neuronal stress and degeneration is activation of microglia, which can proliferate, migrate towards, and phagocytose (ie, engulf and ingest) injured neurons; and they also recruit circulating macrophages to escalate inflammation. Such escalation of inflammation appears to contribute to the progression of age- related macular degeneration (AMD), since AMD is associated with a polymorphism of complement Factor H and drusen are associated with immune complexes and subretinal accumulation of activated microglia and macrophages. The causality and sequence of the escalation of the immune response is unclear. We are developing novel ways to measure inflammation during retinal degeneration (Aim 1) and to assess the consequences of therapeutics on microglial and macrophage dynamics and the rate of degeneration in vivo (Aim 2). The ultimate goal of the work is to be able to delay or prevent photoreceptor degeneration in AMD through manipulation of the early immune response. 

First published on: July 17, 2015

Last modified on: November 29, 2022