Molecular mechanisms of photoreceptor protection in rat models of degenerative retinal disease

Project Aim

This project aimed to understand how the retina defends itself in degenerative retinal diseases by producing protective molecules called trophic factors. It also explored how vision loss is caused not only by the death of retinal cells but also by damage to surviving cells, suggesting that some vision may be restored in patients with retinal degeneration.

Project Summary and Impact

The protective role of trophic factors in the retina were studied and it was found that while they protect cells, they also reduce the retina’s sensitivity to light.
Additionally, it was discovered that vision loss in retinal degeneration is partly due to damage to surviving cells, which may be reversible. By managing light exposure, the team was able to improve visual performance in animal models.

These findings suggest that vision restoration may be possible through non-invasive methods like light manipulation and infrared radiation. This research has influenced ongoing studies and was shared with Retina Australia in 2004.

Published Peer Reviewed Articles

Valter K, Bisti S, Gargini C, Di Loreto S, Maccarone R, Cervetto L, Stone J. Timecourse Of Neurotrophic Factor Upregulation Following Unilateral Optic Nerve Section. Investigative Ophthalmology and Visual Science. 2005, Vol 46: 1748 – 1754.
Stone I, Sandercoe TM, Provis J. Mechanisms of the Formation and Stability of Retinal Blood Vessels. Ocular Angiogenesis, 2006: 101-106.
Yu DY, Cringle S, Valter K, Walsh N, Lee D, Stone J. Photoreceptor death, trophic factor expression, retinal oxygen status, and photoreceptor function in the P23H rat. Invest Ophthalmol Vis Sci. 2004, 45: 2013-2019.
Walsh N, Van Driel D, Lee D, Stone J. Multiple vulnerability of photoreceptors to mesopic ambient light in the P23H transgenic rat. Brain Res. 2004, l013: 194-203.
Stone I, Mervin K, Walsh N, Valter K, Provis I, Penfold P. Photoreceptor stability and degeneration in mammalian retina: lessons from the edge. In: Penfold P, Provis J, eds. Macular Degeneration: Science and Medicine in Practice. Springer Verlag; 2004; 149-165.
Gargini C, Bisti S, Demontis G, Valter K, Stone J, Cervetto L. ERG changes associated with retinal upregulation of trophic factors: observations following optic nerve section. Neuroscience. 2004; 126: 775-783.
Bravo-Nuevo A, Walsh N, Stone J. Photoreceptor degeneration and loss of retinal function in the C57BL/6-C(2J) mouse. In»est Ophthalmol Vis Sci. 2004; 45: 2005-12.
Geller SF, Stone J. Quantitative PCR analysis of FosB mRNA expression after short duration oxygen and light stress. Adv Exp MedBiol. 2003; 533: 249-57.
Bravo-Nuevo A, Williams N, Geller S, Stone J. Mitochondrial deletions in normal and degenerating rat retina. Adv Exp MedBiol. 2003; 533: 241-8.
Valter K, Driel DV, Bisti S, Stone JS. FGFRI Expression and FGFRl-FGF-2 Colocalisation in Rat Retina: Sites of FGF-2 on Rat Photoreceptors. Growth Factors. 2002; 20: 177-188.