Functional Characterization of Mouse RDH11 as a Retinol Dehydrogenase Involved in Dark Adaptation in Vivo

Abstract

We previously cloned mouse RDH11 (mRDH11) as a gene regulated by the transcription factor sterol regulatory element-binding proteins and showed that it is a retinol dehydrogenase expressed in non-ocular tissues such as the liver and testis and in the retina We show by immunoblot analysis that mRDH11 is associated with retinal membranes purified from a non-outer segment fraction of the retina. No obvious retinal defect was found during development and aging of RDH11-deficient mice. The functional consequences of mRDH11 disruption were investigated by electroretinography. Dark adaptation was delayed by a factor of 2.5-3 compared with wild-type mice. However, the kinetics of 11-cis-retinal recycling during dark adaptation was not affected, suggesting that mRDH11 is not involved in the visual cycle. We propose that mRDH11 disruption affects retinoid metabolism in photoreceptor inner segments and delays the kinetics of dark adaptation through modulation of calcium homeostasis.

Targeted Disruption of the Murine Retinal Dehydrogenase Gene Rdh12 Does Not Limit Visual Cycle Function

“…Since Rdh5 knockout mice exhibit very mild visual disturbances (7), it has been suggested that Rdh5 activity may be redundant with that of other isoforms. Consistent with this notion, mice deficient for Rdh11 and for prRdh, two isoforms expressed in the photoreceptors, exhibit a mild phenotype without signs of retinal degeneration (15,16). Functional interaction of RDH5 with RDH11 has been proposed (16), but studies showing that RDH11 is expressed in the photoreceptor cell inner segment complicate this interpretation (15).…”

“…Consistent with this notion, mice deficient for Rdh11 and for prRdh, two isoforms expressed in the photoreceptors, exhibit a mild phenotype without signs of retinal degeneration (15,16). Functional interaction of RDH5 with RDH11 has been proposed (16), but studies showing that RDH11 is expressed in the photoreceptor cell inner segment complicate this interpretation (15). RDH10 is expressed in both the RPE and Müller cells and is specific for the oxidation of all-trans retinol (30).…”

Understanding Retinol Metabolism: Structure and Function of Retinol Dehydrogenases

“…Most notably, mutations in rdh12 have been shown to cause a retinal disease known as Leber's congenital amaurosis, demonstrating that this enzyme is responsible for the reduction of all-trans-retinal into retinol in the photoreceptor cells (19). The proposed role of RDH11 in the visual cycle has, however, been questioned (20), and others (21) have suggested that this enzyme (also referred to as RalR1 or PSDR1) serves as a retinal reductase rather than an oxidizing enzyme, although purely based on in vitro data. This same enzyme has also been implicated in retinoid homeostasis in normal and neoplastic prostate, and its expression seems to be regulated by androgens (22).…”

Rdh12 Activity and Effects on Retinoid Processing in the Murine Retina

“…These studies included generation and analysis of Rdh5-deficient mice lacking the RDH isoform specific to the RPE (17), Rdh11-deficient mice lacking the RDH isoform most closely related to Rdh12 (18,19), and Rdh8-deficient mice lacking the RDH isoform that localizes to photoreceptor outer segments (20). In each case, loss-offunction resulted in only minor slowing of dark adaptation without accompanying retinal degeneration, thus raising the possibility of redundancy in RDH function relative to the visual cycle mechanism.…”