Mechanisms of photoreceptor death and survival in mammalian retina

Jonathan Stone, Juliani Maslim, Krisztina Valter-Kocsi, Mervin Kyle Mervin, Felicity Bowers, Yi Chu, Nigel Barnett, Jan Provis, Geoff Lewis, Steven K. Fisher, Silvia Bisti, Claudia Gargini, Luigi Cervetto, Saul Merin, Jacob Pe'er

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212 Citations (Scopus)

Abstract

The mammalian retina, like the rest of the central nervous system, is highly stable and can maintain its structure and function for the full life of the individual, in humans for many decades. Photoreceptor dystrophies are instances of retinal instability. Many are precipitated by genetic mutations and scores of photoreceptor-lethal mutations have now been identified at the codon level. This review explores the factors which make the photoreceptor more vulnerable to small mutations of its proteins than any other cell of the body, and more vulnerable to environmental factors than any either retinal neurone. These factors include the highly specialised structure and function of the photoreceptors, their high appetite for energy, their self-protective mechanisms and the architecture of their energy supply from the choroidal circulation. Particularly important are the properties of the choroidal circulation, especially its fast flow of near-arterial blood and its inability to autoregulate. Mechanisms which make the retina stable and unstable are then reviewed in three different models of retinal degeneration, retinal detachment, photoreceptor dystrophy and light damage. A two stage model of the genesis of photoreceptor dystrophies is proposed, comprising an initial 'depletion' stage caused by genetic or environmental insult and a second 'late' stage during which oxygen toxicity damages and eventually destroys any photoreceptors which survive the initial depletion. It is a feature of the model that the second 'late' stage of retinal dystrophies is driven by oxygen toxicity. The implications of these ideas for therapy of retinal dystrophies are discussed.

Original languageEnglish
Pages (from-to)689-735
Number of pages47
JournalProgress in Retinal and Eye Research
Volume18
Issue number6
DOIs
Publication statusPublished - 1 Nov 1999
Externally publishedYes

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Retinal Dystrophies
Retina
Mutation
Survival
Oxygen
Retinal Neurons
Retinal Degeneration
Vertebrate Photoreceptor Cells
Appetite
Retinal Detachment
Codon
Central Nervous System
Light
Proteins
Therapeutics

Cite this

Stone, J., Maslim, J., Valter-Kocsi, K., Kyle Mervin, M., Bowers, F., Chu, Y., ... Pe'er, J. (1999). Mechanisms of photoreceptor death and survival in mammalian retina. Progress in Retinal and Eye Research, 18(6), 689-735. https://doi.org/10.1016/S1350-9462(98)00032-9
Stone, Jonathan ; Maslim, Juliani ; Valter-Kocsi, Krisztina ; Kyle Mervin, Mervin ; Bowers, Felicity ; Chu, Yi ; Barnett, Nigel ; Provis, Jan ; Lewis, Geoff ; Fisher, Steven K. ; Bisti, Silvia ; Gargini, Claudia ; Cervetto, Luigi ; Merin, Saul ; Pe'er, Jacob. / Mechanisms of photoreceptor death and survival in mammalian retina. In: Progress in Retinal and Eye Research. 1999 ; Vol. 18, No. 6. pp. 689-735.
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Stone, J, Maslim, J, Valter-Kocsi, K, Kyle Mervin, M, Bowers, F, Chu, Y, Barnett, N, Provis, J, Lewis, G, Fisher, SK, Bisti, S, Gargini, C, Cervetto, L, Merin, S & Pe'er, J 1999, 'Mechanisms of photoreceptor death and survival in mammalian retina' Progress in Retinal and Eye Research, vol. 18, no. 6, pp. 689-735. https://doi.org/10.1016/S1350-9462(98)00032-9

Mechanisms of photoreceptor death and survival in mammalian retina. / Stone, Jonathan; Maslim, Juliani; Valter-Kocsi, Krisztina; Kyle Mervin, Mervin; Bowers, Felicity; Chu, Yi; Barnett, Nigel; Provis, Jan; Lewis, Geoff; Fisher, Steven K.; Bisti, Silvia; Gargini, Claudia; Cervetto, Luigi; Merin, Saul; Pe'er, Jacob.

In: Progress in Retinal and Eye Research, Vol. 18, No. 6, 01.11.1999, p. 689-735.

Research output: Contribution to journalReview articleResearchpeer-review

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T1 - Mechanisms of photoreceptor death and survival in mammalian retina

AU - Stone, Jonathan

AU - Maslim, Juliani

AU - Valter-Kocsi, Krisztina

AU - Kyle Mervin, Mervin

AU - Bowers, Felicity

AU - Chu, Yi

AU - Barnett, Nigel

AU - Provis, Jan

AU - Lewis, Geoff

AU - Fisher, Steven K.

AU - Bisti, Silvia

AU - Gargini, Claudia

AU - Cervetto, Luigi

AU - Merin, Saul

AU - Pe'er, Jacob

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Stone J, Maslim J, Valter-Kocsi K, Kyle Mervin M, Bowers F, Chu Y et al. Mechanisms of photoreceptor death and survival in mammalian retina. Progress in Retinal and Eye Research. 1999 Nov 1;18(6):689-735. https://doi.org/10.1016/S1350-9462(98)00032-9