A hypothesis to explain ganglion cell death caused by vascular insults at the optic nerve head: possible implication for the treatment of glaucoma.

Osborne, N.N.; Melena, José; Chidlow, Glyn; Wood, J. K.

doi:10.1016/s0002-9394(01)01387-3

Cited by 41 publications

(65 citation statements)

References 25 publications

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“…I n 2001 we summarised potential risk factors for retinal ganglion cell (RGC) death in glaucoma, concluding that their vulnerability was affected by reduced blood flow at the optic nerve head. 1 We propose here that light transmitted to the retina is an additional risk factor both for glaucoma (fig 1) and the mitochondrial optic neuropathies (MONs).…”

mentioning

confidence: 97%

A hypothesis to suggest that light is a risk factor in glaucoma and the mitochondrial optic neuropathies

Osborne

Lascaratos

Bron

et al. 2006

British Journal of Ophthalmology

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115

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mentioning

confidence: 97%

A hypothesis to suggest that light is a risk factor in glaucoma and the mitochondrial optic neuropathies

Osborne

Lascaratos

Bron

et al. 2006

British Journal of Ophthalmology

Self Cite

115

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“…Clearly, raised IOP is not synonymous with loss of vision in all glaucoma patients. Many other factors, other than raised IOP, have therefore been proposed to contribute to, or be one of the causes for initiating glaucoma (Osborne et al. 2001, 2006; Flammer et al.…”

mentioning

confidence: 99%

“…2006). Osborne et al. (2001), suggested that once glaucoma is initiated, a bioenergetic defect is established, with the normally functioning ganglion cells being significantly more susceptible to any subsequent insults that ultimately cause them to die, at different times, by apoptosis (Kerrigan et al.…”

mentioning

confidence: 99%

Light affects mitochondria to cause apoptosis to cultured cells: possible relevance to ganglion cell death in certain optic neuropathies

Osborne

et al. 2008

Journal of Neurochemistry

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Retinal ganglion cell axons within the globe are laden with mitochondria that are unprotected from light (400–760 nm) impinging onto the retina. Light can be absorbed by mitochondrial enzymes such as cytochrome and flavin oxidases causing the generation of reactive oxygen species, and we have suggested this may pose a risk to ganglion cell survival if their energy state is compromised, as may be so in glaucoma or in Leber’s Hereditary Optic Neuropathy. Here, we demonstrate that light (400–760 nm) provokes apoptosis in cultured retinal ganglion‐5 cells, and that this effect is enhanced in low serum, and attenuated by various antioxidants. Apoptosis is shown to be caspase independent, involving reactive oxygen species generation and the activation of poly(ADP‐ribose) polymerase‐1 and apoptosis‐inducing factor. We further show that light‐induced apoptosis requires the participation of the mitochondrial respiratory chain. This was demonstrated by culturing fibroblasts (BJhTERT cells) in ethidium bromide for 40 days to deplete their mitochondrial DNA and perturb their mitochondrial respiratory chain function (BJhTERT rh0 cells). Only BJhTERT cells, with intact mitochondrial respiratory chain function were affected by light insult. Finally, we show that exposure of anaesthetized pigmented rat eye to white, but not red light, causes changes in the expression of certain retinal mRNAs (neurofilament light, Thy‐1 and melanopsin) and optic nerve proteins (neurofilament light and tubulin), suggesting that ganglion cell survival is affected. Our findings support the proposal that the interaction of light, particularly the blue component, with intra‐axonal ganglion cell mitochondria may be deleterious under certain circumstances, and suggest that reducing the light energy impinging upon the retina might benefit patients with certain optic neuropathies.

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“…According to the vasogenic theory, raised IOP may also disturb the quality of the blood supply to the ONH, leading to hypoxia and reduced nutrition to optic nerve axons, 18 which ultimately leads to ganglion cell death. Alterations in the quality of the blood supply to the optic nerve head can also be induced by factors that are independent of IOP, e.g.…”

Section: Vasogenicmentioning

confidence: 99%

Histopathology and pathogenesis of glaucomatous optic neuropathy

Lawrenson¹

2007

Glaucoma Identification &Amp; Co-Management

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A hypothesis to explain ganglion cell death caused by vascular insults at the optic nerve head: possible implication for the treatment of glaucoma.

Cited by 41 publications

References 25 publications

A hypothesis to suggest that light is a risk factor in glaucoma and the mitochondrial optic neuropathies

A hypothesis to suggest that light is a risk factor in glaucoma and the mitochondrial optic neuropathies

Light affects mitochondria to cause apoptosis to cultured cells: possible relevance to ganglion cell death in certain optic neuropathies

Histopathology and pathogenesis of glaucomatous optic neuropathy

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