No evidence for loss of short-wavelength sensitive cone photoreceptors in normal ageing of the primate retina

Abstract

In old world primates including humans, cone photoreceptors are classified according to their maximal sensitivity at either short (S, blue), middle (M, green) or long (L, red) wavelengths. Colour discrimination studies show that the S-cone pathway is selectively affected by age and disease, and psychophysical models implicate their loss. Photoreceptors have high metabolic demand and are susceptible to age or disease-related losses in oxygen and nutrient supply. Hence 30% of rods are lost over life. While comparable losses are not seen in cones, S-cones comprise less than 10% of the cone population, so significant loss would be undetected in total counts. Here we examine young and aged primate retinae stained to distinguish S from M/L-cones. We show there is no age-related cone loss in either cone type and that S-cones are as regularly distributed in old as young primates. We propose that S-cone metabolism is less flexible than in their M/L counterparts, making them more susceptible to deficits in normal cellular function. Hypoxia is a feature of the ageing retina as extracellular debris accumulates between photoreceptors and their blood supply which likely impacts S-cone function. However, that these cells remain in the ageing retina suggests the potential for functional restoration.

Mitochondrial absorption of short wavelength light drives primate blue retinal cones into glycolysis which may increase their pace of aging

“…It is assumed that increased VDAC expression promotes cell death, while reduced expression is associated with cell survival 12 . The reduced VDAC levels are consistent with S-cones survival with age in primates 11 . Hence, S-opsin cones have relatively few mitochondria and do not express pyruvate dehydrogenase, which is a key marker of mitochondrial respiration.…”

“…Although their number does not decline with age 11 , they are functionally vulnerable 5 . We ask if these unique characteristics result from fundamental metabolic differences.…”

“…Such processes may underpin the selective early decline in aged human S-cone function. As primate S-cones are not lost with age 11 , their functional decline is likely due to their distinct metabolism.…”

Primate retinal cones express phosphorylated tau associated with neuronal degeneration yet survive in old age

“…Here aged decline is apparent in both rod and cone mediated visual function ( Birch and Anderson, 1992 ) and significant rod loss in the central retina is established by around 70 years of age. However, there is no evidence for age related cone loss not even among short wavelength sensitive cones that show the greatest functional vulnerability ( Curcio et al., 1993 ; Weinrich et al., 2017 ). Even with the development of aged retinal disease, such as age-related macular degeneration, central cones show marked resistance to apoptosis even when the rod population around them has been lost due to geographic atrophy and their own function has declined ( Curcio et al., 1996 ).…”

Retinal photoreceptor and ganglion cell types and topographies in the red fox (Vulpes vulpes) and Arctic fox (Vulpes lagopus)

“…In humans, a specific loss of short‐wavelength sensitivity occurs during aging (Haegerstrom‐Portnoy, Hewlett, & Barr, ), and photoreceptor numbers are reduced during aging (Curcio, Millican, Allen, & Kalina, ; Gao & Hollyfield, ). A study on primates suggests, however, that S cone function rather than absolute numbers are selectively affected by age (Weinrich et al, ). Thus, no definite conclusion can be drawn about whether the low S cone density in VV8 represents age‐related or disease‐induced degeneration, or just inter‐individual variation.…”