Research in the Jastrzebska lab focuses on understanding the underlying molecular mechanisms of retinal degenerative diseases associated with compromised rhodopsin regeneration. The animal visual receptor rhodopsin is composed of an apoprotein opsin covalently bound to the vitamin A-derived chromophore, 11-cis-retinal. Rhodopsin activation includes chromophore isomerization to its all-trans stereoisomer, its subsequent release and recycling in a series of enzymatic reactions called the ‘retinoid or visual’ cycle. Dysfunction of enzymes involved in this cycle can impair rhodopsin regeneration and affect visual function. Regeneration of rhodopsin is compromised in several retinal disorders. Novel, non-hydrolysable chromophore analogues are tested in context of potential therapeutic strategies to protect retinal health in these visual impairments. The effects of selected retinal analogues are tested in vitro and in vivo, in model animals. To better understand the molecular basis of these retinopathies and to delineate the molecular physiology of the protective effects mediated by the new retinal analogues, the whole eye transcriptome analyses and gene targeted analyses are being developed. These high-throughput analyses provide a comprehensive snapshots of the biological state of the cellular system providing a foundation to identify novel factors involved in drug mediated protection against light-induced retinopathies.
Additional areas of research in the laboratory include investigation of the structure and function of the visual G protein coupled receptors (GPCRs) under physiological and pathological conditions. Rhodopsin is not only a fundamental molecule in our visual system that transmits the light signal to the brain, but it is also associated with diseases affecting human eyesight like retinitis pigmentosa, retinal degeneration, and night blindness. Therefore, efforts are directed towards understanding the molecular basis of these inherited impairments using biochemical, biophysical, and structural methods. This research aims to make groundbreaking progress in developing molecule modulators that can effectively target visual GPCRs and prevent disease phenotypes.