Phosphoinositide metabolism in Drosophila phototransduction: a coffee break discussion leads to 30 years of history.

The aim of this review is to summarize the history of Dr. Yoshiki Hotta and his collaborators' contributions to the research field of Drosophila phototransduction. The electroretinogram-defective mutants reported in 1970 by Dr. Hotta and Dr. Seymour Benzer in the article entitled "Genetic dissection of the Drosophila nervous system by means of mosaics" have attracted the interest of many researchers, and have been used as a great tool to dissect the mechanisms underlying phototransduction. The early collaboration of Dr. Hotta with the group of Dr. Tohru Yoshioka, who was studying the roles of phosphoinositides in the nervous system biochemically, combined biochemical and genetic approaches to phototransduction-defective no receptor potential A (norpA) and retinal degeneration A (rdgA) mutants, which led to the hypothesis that phosphoinositide metabolism regulates phototransduction in Drosophila. This was proven later by the identification of the norpA and rdgA mutant genes, which encode phospholipase C and diacylglycerol kinase, respectively. Thus the collaboration of Dr. Hotta and Dr. Yoshioka laid the foundation of our understanding of the role of phosphoinositide metabolism in Drosophila phototransduction. In addition, a collaboration carried out with the group of Dr. Kazushige Hirosawa on the ultrastructural analyses of retinal degeneration mutants, rdgA and rdgB, led to the discovery of the subcellular membrane organelle called submicrovillar cisternae, which is involved in the phosphoinositide metabolism. In this review, the authors will summarize these results, which were inspired by Dr. Hotta's insights.

[Identification of the molecular bases of retinal dystrophies: two divergent situations and their implications]. / Identification des bases moléculaires des dystrophies rétiniennes héréditaires: découverte de vérités contraires et conséquences.

In industrialized countries inherited retinal dystrophies are the leading cause of legal blindness across all ages, together with age-related macular degeneration. Most retinal dystrophies were first described between the end of the 19th century and the beginning of the 20th century as "chorioretinal heredodegenerations". This term is now obsolete, although it has the merit of mentioning the ineluctably degenerative nature of these inherited blinding disorders. These diseases are now known to be highly heterogeneous, both clinically and genetically. However, their molecular bases remained a mystery until the early 1980s, when the advent of genetic engineering offered the possibility of mapping and identifying genes of unknown structure and function. Within a few decades, better knowledge of the molecular bases of retinal dystrophies led to significant medical and genetic advances. Two divergent situations were encountered. First, several phenotypes previously thought to be different clinical entities have been united through the identification of mutations in the same gene. Conversely, some other disorders have turned out to comprise two or more genetically and pathophysiologically distinct entities. This rapid progress in medical knowledge has profoundly modified the relationship between patients and caregivers, sound scientific information being the first form of care for patients with incurable diseases. The genetic deciphering of two diseases, Leber congenital amaurosis and Stargardt disease, represents a good example of how basic knowledge and the patient-carer relationship have evolved in recent decades.

Leber congenital amaurosis: from darkness to spotlight.

Almost 150 years ago, Theodor Leber described a severe form of vision loss at or near birth which was later given his name. During the century that followed this description, ophthalmologists dedicated efforts to give an accurate definition of the disease but patients were neglected because of the inability of physicians to provide them with treatment. In the 90s, at the time of the Golden Age of Linkage, the first LCA locus was mapped to a human chromosome and shortly after identified as the gene for guanylate cyclase. This discovery was the spark that made the disease emerge from the shadows as illustrated by the flood of LCA genes identified in the following ten-year period. During the same time period, the clinical variability of the disease was rediscovered and an unexpected physiopathological heterogeneity demonstrated. In the beginning of the third millennium, LCA came out definitively from the tunnel to shine under the bright spotlights with the RPE65 gene therapy trial that succeeded to restore vision in a dog model and opened the door to gene therapy trials in humans.

Did Edgar Degas have an inherited retinal degeneration?

OBJECTIVE: Retrospective analysis of the famous painter Edgar Degas' eye disease. DESIGN: A historical review and analysis based on Degas' paintings and letters exchanged between the painter and his friends and family members, as well as on the chronicles of his associates. DeGas-Musson family papers at the Howard-Tilton Library of Tulane University are also reviewed. RESULTS: Degas had an eye disease that was first noticed in 1870 and that progressed throughout his life. He suffered from progressive bilateral central visual loss and light sensitivity which was most acutely recognized while he was visiting his mother's side of the family in New Orleans where he could not paint outside because of the bright sun. Edgar's maternal first cousin, Estelle Musson, also suffered gradual bilateral visual loss, and was also known to have light sensitivity early in her life. Estelle became totally blind in her early 30s. Both Edgar and Estelle were otherwise healthy and lived long lives. CONCLUSION: It is likely that Edgar Degas and his cousin Estelle Musson had a hereditary retinal degeneration primarily affecting their central vision. Degas' retinal disease undoubtedly affected his life and his art but did not prevent him from being one of the most admired painters of all times.