SUMMARY OF RESEARCH DURING 2011
(2MD's/PhD's, 10 MD’s; 9 PhD’s; 2 other; 69 publications; 1 book and 12 book chapters distributed in 4 books)
Significant Scientific Accomplishments
We continue to expand our understanding of how interactions between retinal metabolism, environmental stress and genetic mutations lead to blindness through 3 major research areas.
- The bis-retinoid, A2E, has been implicated in various forms of Human Retinal Degeneration. With newly developed imaging techniques, we have measured the distribution of A2E across the retinal pigment epithelium in humans. We have determined that A2E is not a major contributor to lipofuscin in humans, as the patterns of distribution do not correlate. There is considerable ongoing research to develop methods that will reduce A2E, and therefore lipofuscin in humans. Our results indicate that A2E is not a major component of lipofuscin. Therefore, these approaches merit reconsideration.
- The neuroprotective effects of opioid-receptor-agonists against Glaucomatous Retinal Injury were investigated. In both in vitro and in vivo studies in several species, delta-opioid-receptor activation was found to be protective of retinal function and enhanced retinal ganglion cell survival against glaucomatous injury. Delta-opioid-receptor agonists have a potential to be used clinically to treat glaucoma and merit further study.
- Neuroinflammation and the activation of the complement cascade have been implicated in a number of neurodegenerative diseases, including Age-related macular degeneration (AMD). We are investigating the mechanism of photoreceptor degeneration and neuroprotection with a focus on the role of complement using a number of in vitro and in vivo models. We have confirmed that pathological activation of the alternative pathway of complement is required, but not sufficient in animal models of AMD. This is a critical finding and we are currently investigating how the classical and lectin pathways contribute to initiating the disease. Understanding the contribution of the complement cascade to AMD pathology has the potential to open avenues of novel treatment strategies for AMD.