Dark Adaptation and Its Role in Age-Related Macular Degeneration

Abstract

Dark adaptation (DA) refers to the slow recovery of visual sensitivity in darkness following exposure to intense or prolonged illumination, which bleaches a significant amount of the rhodopsin. This natural process also offers an opportunity to understand cellular function in the outer retina and evaluate for presence of disease. How our eyes adapt to darkness can be a key indicator of retinal health, which can be altered in the presence of certain diseases, such as age-related macular degeneration (AMD). A specific focus on clinical aspects of DA measurement and its significance to furthering our understanding of AMD has revealed essential findings underlying the pathobiology of the disease. The process of dark adaptation involves phototransduction taking place mainly between the photoreceptor outer segments and the retinal pigment epithelial (RPE) layer. DA occurs over a large range of luminance and is modulated by both cone and rod photoreceptors. In the photopic ranges, rods are saturated and cone cells adapt to the high luminance levels. However, under scotopic ranges, cones are unable to respond to the dim luminance and rods modulate the responses to lower levels of light as they can respond to even a single photon. Since the cone visual cycle is also based on the Muller cells, measuring the impairment in rod-based dark adaptation is thought to be particularly relevant to diseases such as AMD, which involves both photoreceptors and RPE. Dark adaptation parameters are metrics derived from curve-fitting dark adaptation sensitivities over time and can represent specific cellular function. Parameters such as the cone-rod break (CRB) and rod intercept time (RIT) are particularly sensitive to changes in the outer retina. There is some structural and functional continuum between normal aging and the AMD pathology. Many studies have shown an increase of the rod intercept time (RIT), i.e., delays in rod-mediated DA in AMD patients with increasing disease severity determined by increased drusen grade, pigment changes and the presence of subretinal drusenoid deposits (SDD) and association with certain morphological features in the peripheral retina. Specifications of spatial testing location, repeatability of the testing, ease and availability of the testing device in clinical settings, and test duration in elderly population are also important. We provide a detailed overview in light of all these factors.

Cone Photoreceptor Loss in Light-Damaged Albino Rats

“…Many human retinal diseases present in the fourth decade and beyond, and thus the sustainability of retinal signaling and the opportunity for intervention in this type of animal model offers great opportunity to test interventions before, during, and after the degenerative stress. This approach is also relevant for AMD, which arises from a lifetime of photoreceptor activity, oxidative stress, and metabolic challenge and which attacks the rods first but ultimately results in catastrophic loss of cone-dependent vision [ 39 ], excellently reviews by Nigayle et al (2022) [ 40 ].…”

Watching the human retina breath in real time; the slowing of mitochondrial respiration with age in dark adaptation

“…The process of dark adaptation is disrupted in AMD 19,39 , a disease of ageing which has an association with mitochondrial dysfunction. Animal models of AMD have clear mitochondrial abnormalities from early retinal differentiation onward 40 , while RPE cells collected from AMD patients have mitochondrial respiratory abnormalities 41 .…”

“…While it is known that the dark adaptation function measured by rod intercept time is delayed with age [18][19][20]36 , the extent of the difference between the two age groups in terms of the mitochondrial response in the rst 3 min is unexpected. It would appear that mitochondria in the ageing group failed to show any increase in metabolism when challenged.…”

“…Here mitochondria are stressed because of the increased demand for adenosine triphosphate (ATP) to support changes in retinal sensitivity 2,4 . Dark adaptation is a standard metric for visual function assessment and reveals abnormalities in ageing that can be a precursor to retinal disease [18][19][20] . However, the physiological and metabolic platform of this has never been revealed.…”

Histology of type 3 macular neovascularization and microvascular anomalies in treated age-related macular degeneration: a case study

“…The area of type 3 MNV vulnerability in the ETDRS inner ring is just peripheral to the foveal avascular zone 46 on the inner slope of the crest of high rod density, where rod vision is poor in AMD eyes. [47][48][49][50][51] Metabolic demand of foveal cones is very high, and choriocapillaris OCTA signal decreases under the fovea throughout adulthood. 52,53 It is thus possible that the distribution of type 3 MNV is a bystander effect from changes under the fovea that also lead to high-risk drusen.…”