A novel cone visual cycle in the cone-dominated retina

Abstract

The visual processing of humans is primarily reliant upon the sensitivity of cone photoreceptors to light during daylight conditions. This underscores the importance of understanding how cone photoreceptors maintain the ability to detect light. The vertebrate retina consists of a combination of both rod and cone photoreceptors. Subsequent to light exposure, both rod and cone photoreceptors are dependent upon the recycling of vitamin A to regenerate photopigments, the proteins responsible for detecting light. Metabolic processing of vitamin A in support of rod photopigment renewal, the so-called "rod visual cycle", is well established. However, the metabolic processing of vitamin A in support of cone photopigment renewal remains a challenge for characterization in the recently discovered "cone visual cycle". In this review we summarize the research that has defined the rod visual cycle and our current concept of the novel cone visual cycle. Here, we highlight the research that supports the existence of a functional cone-specific visual cycle: the identification of novel enzymatic activities that contribute to retinoid recycling, the observation of vitamin A recycling in cone-dominated retinas, and the localization of some of these activities to the Müller cell. In the opinions of the authors, additional research on the possible interactions between these two visual cycles in the duplex retina is needed to understand visual detection in the human retina.

Identification of the 11- cis- specific retinyl-ester synthase in retinal Müller cells as multifunctional O- acyltransferase (MFAT)

“…Retinas from cone-dominant species contain 11-cis-retinyl esters (11-cis-REs), whereas retinyl esters are much less abundant in retinas from rod-dominant species (11,13,15). Homogenates from cone-dominant chicken and ground-squirrel retinas convert all-trans-ROL predominantly to 11-cis-REs in the presence of palmitoyl CoA (palm CoA) (13,16,17). These observations suggest that selective esterification of 11-cis-ROL may be the driving force for 11-cis-retinoid formation.…”

Parallel visual cycles in the zebrafish retina

“…However, only fairly recent mostly biochemical studies conducted in cone-dominant species such as chicken and ground squirrel have confirmed this concept (Muniz et al, 2007).…”

“…This competition is aggravated by the rods being driven into saturation under photopic conditions with a maximal demand for pigment regeneration. As rod and cone photoreceptors compete for 11-cis RAL, the high demand for visual pigment by rod photoreceptors under photopic conditions might therefore restrict the availability of chromophore to cone photoreceptors in their working range (Mata et al, 2002;Muniz et al, 2007). Samardzija et al created an RPE65 knock-in mouse model carrying the R91W mutation to investigate the consequences of chromophore insufficiency on cone function (Samardzija et al, 2009).…”

“…Bunt-Milam and Saari, 1983;Fong et al, 1984;Jin et al, 2009;Lamb and Pugh, 2006;Parker et al, 2009;Pepperberg et al, 1993). For a comprehensive review of the intra-retinal visual cycle please refer to (Muniz et al, 2007).…”

Evolution and the origin of the visual retinoid cycle in vertebrates

“…Until now, there is no direct in vivo evidence that Mü ller cells provide visual retinoid for cone vision. The all-trans-ROL isomerase expressed in Mü ller cells is distinct from RPE65 isomerase, because the former converts all-trans-ROL to 11-cis-ROL (Mata et al 2002(Mata et al , 2005Muniz et al 2007), whereas the latter uses all-trans-RP as its substrate. In another study, it was shown that only all-trans-RP is the direct precursor of 11-cis-ROL in chicken RPE/retina mixture membranes, suggesting that RPE65 may be involved in the synthesis of 11-cis-ROL in the chicken retina (Gollapalli & Rando 2003).…”