Differential Effects of Light and Alcohol on the Electro-oculographic Responses of Patients with Age-Related Macular Disease

Arden, G B; Wolf, Janet E.

doi:10.1167/iovs.02-0998

Cited by 28 publications

(33 citation statements)

References 34 publications

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“…Outer retina hypoxia may be further enhanced by decreased diffusion of oxygen from the choroid to the RPE and retina, caused by the age-related changes in Bruch's membrane [8,10,27]. This is supported by recent studies indicating decreased diffusion of ethanol, a molecule only slightly larger than oxygen, through Bruch's membrane in eyes with AMD [6].…”

Section: Role Of the Rpe In The Pathogenesis Of Cnvmentioning

confidence: 72%

Role of growth factors and the wound healing response in age-related macular degeneration

Schlingemann

2003

Graefe's Arch Clin Exp Ophthalmol

252

193

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Growth factors (GF) are important in several stages of the pathogenesis of age-related macular disease (AMD). In choroidal neovascularization (CNV) in exudative AMD, the GF involved are similar to those involved in wound healing of the skin. Like granulation tissue of skin, CNV is characterized by clotting, inflammation, angiogenesis and fibrosis, and like in skin wounds, members of the VEGF, angiopoietin, PDGF and TGF-beta families of GF are expressed. However, several of these GF may also serve physiological functions in the normal eye, where the retinal pigment epithelium (RPE) employs them to provide trophic support to the neuroretina and choriocapillaris, in addition to maintaining an anti-angiogenic state. Derangement of these physiological functions may underlie the initiation of CNV in AMD. Basolateral secretion of VEGF-A by the RPE maintains the choriocapillaris, and is enhanced by hypoxia. Age-related changes in Bruch's membrane lead to impairment of this trophic function and choriocapillaris atrophy, as well as to decreased diffusion of oxygen towards the neuroretina. The resulting outer retina hypoxia may be an important driving force of CNV formation, by stimulating VEGF overexpression by the RPE, in addition to the effects of increased oxidative stress and low-grade inflammation. RPE senescence and hypoxia may also decrease expression of angiogenesis inhibitors such as PEDF, further shifting the balance to a pro-angiogenic state in the aging eye.

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Section: Role Of the Rpe In The Pathogenesis Of Cnvmentioning

confidence: 72%

Role of growth factors and the wound healing response in age-related macular degeneration

Schlingemann

2003

Graefe's Arch Clin Exp Ophthalmol

252

193

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“…And the majority of AMD patients experience severe vision loss due to the development of choroidal neovascularization (CNV). Reports show that age-related changes in Bruch’s membrane cause hypoxia in the outer retina from choriocapillaris atrophy, and hypoxia may play a role on retinal pigment epithelium (RPE) to initiate the CNV response [1]. The RPE cells could respond with increased basal secretion of vascular endothelial growth factor (VEGF) [2], which will accumulate due to the barrier properties of the thickened, lipid-laden Bruch membrane [3].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of VEGF Expression by Targeting HIF-1α with Small Interference RNA in Human RPE Cells

et al. 2007

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Background: Vascular endothelial growth factor (VEGF) is upregulated by hypoxia and is a major stimulatory factor for choroidal neovascularization. The upregulation of VEGF expression in response to hypoxia occurs through hypoxia-inducible factor 1 (HIF-1), which is a transcription factor that regulates genes involved in the response to hypoxia. HIF-1α is the inducible subunit of the HIF-1. Aims: To further define HIF-1 function in angiogenesis and to explore novel approaches to modulate choroidal neovascularization in age-related macular degeneration. Methods: In this study, we examined the response of human retinal pigment epithelium (RPE) cells to hypoxia and employed the small interference RNA technique to knock down gene expression of HIF-1α in RPE cells. Results: We found that both the mRNA and protein levels of HIF-1α in the RPE cells increased in response to hypoxia, followed by increasing expression of VEGF. Both the mRNA and protein levels of HIF-1α and VEGF in the RPE cells were decreased dramatically after transfection with a HIF-1α-specific small interference RNA vector. Conclusion: Our results suggest that HIF-1 may be involved in angiogenesis by controlling the expression of VEGF in vivo and provide a possible strategy for the treatment of angiogenesis by targeting the HIF-1α in ischemic retinopathies.

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“…However barriers between the choroidal circulation and the RPE could selectively affect the alcohol-EOG. This apparently is what occurs in Age-related Macular Degeneration, where basal linear deposits and basal laminar deposits [30] and a relatively impermeable Bruch's membrane [31,32] cause a selective reduction in the alcohol response while the light response is relatively normal [16].…”

Section: Implications For Clinical Usementioning

confidence: 85%

“…The oldest subject (#1, #3 & #4) has semi-saturation values slightly higher than the subject 40 years younger (#5) but the amplitudes of his responses are the same as that of a number of young normals. For age relationships see [16].…”

Section: Resultsmentioning

confidence: 99%

“…Most of the alcohol reaching the RPE must come from the choroidal circulation rather than the retinal circulation because of its greater volume, and flow, and proximity to the RPE [16]. Consistent with this, the alcohol EOG is present (Singbartl and Rudolph, personal communication) when in Best's disease a barrier exists between retina and RPE that prevents the development of the light-EOG [17][18][19][20].…”

Section: Introductionmentioning

confidence: 97%

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Two components of the human alcohol electro-oculogram

Wolf¹,

Arden²

2004

Doc Ophthalmol

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Light onset or drinking alcohol causes the standing potential of the eye to rise and then fall to a trough (the EOG). After allowing for the time for the alcohol to be absorbed into the blood stream, the changes of current with time are identical for the two agents but each acts through a separate pathway, on the same effector mechanism. We have shown that +ve and -ve processes of the alcohol-EOG may be differentially affected in disease. We have now determined the separate dose-response relationship of the two voltage changes. Alcohol diluted with water was given by mouth to fasting dark-adapted subjects. Recordings continued until both the positive peak and the later negative trough were well-characterised. Doses of alcohol ranged from 3.54 to 450 mg Kg(-1) of body weight. Experiments were carried out on three normal subjects, 4-8th decade. The results are consistent with the hypothesis that each voltage change is determined by the relation: [EtOH] x [R] <--> [EtOH.R], where <--> represents a reversible reaction. For the +ve peak, semi-saturation occurs at approximately 35 mg Kg(-l). For the -ve trough it is smaller, 11 mg Kg(-l). Therefore the result is consistent with there being 2 distinct processes, and the human EOG cannot be a single 'damped oscillation'. During the short period when change of blood alcohol concentration is effective in causing the EOG sequence (using doses which provoke large voltage changes), the computed blood concentration varies from 0.01 to 0.1 mM, i.e. is > 2 orders of magnitude less than the levels required for intoxication.

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Differential Effects of Light and Alcohol on the Electro-oculographic Responses of Patients with Age-Related Macular Disease

Cited by 28 publications

References 34 publications

Role of growth factors and the wound healing response in age-related macular degeneration

Role of growth factors and the wound healing response in age-related macular degeneration

Inhibition of VEGF Expression by Targeting HIF-1α with Small Interference RNA in Human RPE Cells

Two components of the human alcohol electro-oculogram

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