The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65

Mutations in the MYO7A gene cause a deaf-blindness disorder, known as Usher syndrome 1B.  In the retina, the majority of MYO7A is in the retinal pigmented epithelium (RPE), where many of the reactions of the visual retinoid cycle take place.  We have observed that the retinas of Myo7a-mutant mice are resistant to acute light damage. In exploring the basis of this resistance, we found that Myo7a-mutant mice have lower levels of RPE65, the RPE isomerase that has a key role in the retinoid cycle.  We show for the first time that RPE65 normally undergoes a light-dependent translocation to become more concentrated in the central region of the RPE cells.  This translocation requires MYO7A, so that, in Myo7a-mutant mice, RPE65 is partly mislocalized in the light.  RPE65 is degraded more quickly in Myo7a-mutant mice, perhaps due to its mislocalization, providing a plausible explanation for its lower levels.  Following a 50–60% photobleach, Myo7a-mutant retinas exhibited increased all-trans-retinyl ester levels during the initial stages of dark recovery, consistent with a deficiency in RPE65 activity.  Lastly, MYO7A and RPE65 were co-immunoprecipitated from RPE cell lysate by antibodies against either of the proteins, and the two proteins were partly colocalized, suggesting a direct or indirect interaction.  Together, the results support a role for MYO7A in the translocation of RPE65, illustrating the involvement of a molecular motor in the spatiotemporal organization of the retinoid cycle in vision

New insights and changing paradigms in the regulation of vitamin A metabolism in development

This is the peer reviewed version of the following article: Shannon, S. R., Moise, A. R., & Trainor, P. A. (2017). New insights and changing paradigms in the regulation of vitamin A metabolism in development. Wiley Interdisciplinary Reviews. Developmental Biology, 6(3), 10.1002/wdev.264, which has been published in final form at http://doi.org/10.1002/wdev.264 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Vitamin A and its active metabolite retinoic acid are essential for embryonic development and adult homeostasis. Surprisingly, excess or deficiency of vitamin A and retinoic acid can cause similar developmental defects. Therefore, strict feedback and other mechanisms exist to regulate the levels of retinoic acid within a narrow physiological range. The oxidation of vitamin A to retinal has recently been established as a critical nodal point in the synthesis of retinoic acid, and over the past decade, RDH10 and DHRS3 have emerged as the predominant enzymes that regulate this reversible reaction. Together they form a codependent complex that facilitates negative feedback maintenance of retinoic acid levels and thus guard against the effects of dysregulated vitamin A metabolism and retinoic acid synthesis. This review focuses on advances in our understanding of the roles of Rdh10 and Dhrs3 and their impact on development and disease

Vitamin A Metabolism: An Update

Retinoids are required for maintaining many essential physiological processes in the body, including normal growth and development, normal vision, a healthy immune system, normal reproduction, and healthy skin and barrier functions. In excess of 500 genes are thought to be regulated by retinoic acid. 11-cis-retinal serves as the visual chromophore in vision. The body must acquire retinoid from the diet in order to maintain these essential physiological processes. Retinoid metabolism is complex and involves many different retinoid forms, including retinyl esters, retinol, retinal, retinoic acid and oxidized and conjugated metabolites of both retinol and retinoic acid. In addition, retinoid metabolism involves many carrier proteins and enzymes that are specific to retinoid metabolism, as well as other proteins which may be involved in mediating also triglyceride and/or cholesterol metabolism. This review will focus on recent advances for understanding retinoid metabolism that have taken place in the last ten to fifteen years

Beauveria bassiana as an endophyte: a critical review on associated methodology and biocontrol potential

© 2016, International Organization for Biological Control (IOBC).In the last decade there has been increased focus on the potential of endophytic Beauveria bassiana for the biocontrol of insect herbivores. Generally, detection of endophytes is acknowledged to be problematic and recovery method-dependent. Herein, we critically analyse the methodology reported for the detection of B. bassiana as endophytes following experimental inoculation. In light of the methodology, we further review the effects of endophytic B. bassiana on insect herbivores. Our review indicated the need for stringent protocols for surface sterilisation including thorough experimental controls. For molecular detection protocols by PCR, residual DNA from surface inocula must also be considered. The biocontrol potential of B. bassiana endophytes appears promising although both negative and neutral effects on insect herbivores were reported and there remains ambiguity with respect to the location and mode of action of the fungus in planta. We recommend that future studies adopt multiple techniques, including culture dependent and independent techniques for endophyte detection and elucidate the mechanisms involved against insect herbivores

Parallel visual cycles in the zebrafish retina

Vertebrate vision necessitates continuous recycling of the chromophore 11-cis retinal (RAL). The classical (or canonical) visual cycle employs a number of enzymes located in the photoreceptor outer segment and RPE (retinal pigment epithelium) of the retina to regenerate 11-cis RAL from all-trans RAL. Cone-dominant species are believed to utilize a second, intra-retinal, pathway for 11-cis RAL generation, involving retinal Müller glia cells. This review summarizes the efforts made in zebrafish to gain a better understanding of the role of these two visual cycles for rod and cone photoreceptor chromophore recycling