Bottlenecks in the Investigation of Retinal Sterol Homeostasis

Abstract

Sterol homeostasis in mammalian cells and tissues involves balancing three fundamental processes: de novo sterol biosynthesis; sterol import (e.g., from blood-borne lipoproteins); and sterol export. In complex tissues, composed of multiple different cell types (such as the retina), import and export also may involve intratissue, intercellular sterol exchange. Disruption of any of these processes can result in pathologies that impact the normal structure and function of the retina. Here, we provide a brief overview of what is known currently about sterol homeostasis in the vertebrate retina and offer a proposed path for future experimental work to further our understanding of these processes, with relevance to the development of novel therapeutic interventions for human diseases involving defective sterol homeostasis.

Updates on protein-prenylation and associated inherited retinopathies

“…However, stimulating the synthesis of prenyl groups in the retina may cause undesirable side effects, such as neoplastic growth as is the case with overexpression of prenylated Ras oncogenes products. It is also difficult to predict the impact on isoprene synthesis with this approach given there are multiple feedback mechanisms that regulates mevalonate pathway ( 18 , 184 ). So far, gene augmentation via lentiviral vectors and more recently, episomal scaffold/matrix attachment region (S/MAR)-based plasmid vectors seem to offer promising avenues in the treatment of prenylation-associated retinopathy such as CHM.…”