[Eye connective tissues: cornea and vitreous body]. / Recherches sur les tissus conjonctifs oculaires. La cornée et le corps vitré

The authors, ophtalmologist (Y.P.) and basic scientists (J.L.-R and L.R.), collaborated on eye-research since 1962 on normal and pathological aspects of eye tissues, considered as specialized forms of connective tissues, and on specific aspects of the physiology and pathology of the eye. This date coincides with the foundation of the French Society of Connective Tissues, which celebrates the 50th anniversary of its creation. We shall present here some of our work on the ontogenetic and phylogenetic aspects of the cornea, on its structure, function and regulation in normal and pathological states, taken from a large number of publications of our laboratories. Our work on cornea started with the study of the morphogenesis of its lamellar structure, made of collagen fibers and proteoglycans. This led us to the isolation and characterization of structural (or matrix) glycoproteins, a new class of matrix components, present also in all other connective tissues, and to the study of their biosynthesis by keratocytes. Corneal wounds and regeneration were also studied, as well as some corneal pathologies such as keratoconus. The confrontation of quantitative morphological methods with biochemical procedures were to yield important results on the mechanisms of the maintenance of corneal structure and function. Another series of studies concerned the vitreous where we detected, besides previously characterized components, such as hyaluronan and collagens, fibronectin which plays an important role in the adhesion of hyaluronan to the collagen network. Its age-dependent modifications were also studied, with a special focus on the role of reactive oxygen species (ROS)-mediated degradation of hyaluronan, especially important for the aging of the vitreous.

H244R VSX1 is associated with selective cone ON bipolar cell dysfunction and macular degeneration in a PPCD family.

PURPOSE: To elucidate the retinal dysfunction and the molecular basis of posterior polymorphous corneal dystrophy (PPCD) associated with macular dystrophy, both inherited in a dominant manner through a three-generation family. METHODS: Ophthalmologic examinations including slit lamp examination, visual acuity tests, fundus visualization by scanning laser ophthalmoscopy, fluorescein angiography, color vision tests, electro-oculography, photopic and scotopic electroretinography (ERG) according to the International Society for Clinical Electrophysiology of Vision (ISCEV) protocols, and oscillatory potential (OP) recordings were conducted on affected family members. Corneal button from one affected patient was examined by transmission electron microscopy. All exons and intron-exon boundaries of the VSX1 and the COL8A2 genes were amplified by polymerase chain reaction and sequenced. RESULTS: The presence of endothelial cells that have epithelial-like features with multiple layers, desmosomal junctions, and microvillous projections supports the diagnosis of PPCD. Sequence analysis indicated that the H244R variant in the VSX1 segregated with corneal and macular disease phenotypes in this family. Electrophysiologic studies indicated normal scotopic ERG findings, decreased amplitude of the photopic b-wave, photopic OP2 and OP3 barely recordable with a preserved OP4 amplitude, and variably decreased 30-Hz flicker amplitude. CONCLUSIONS: The human VSX1 is required for cone ON bipolar cell function but not for rod and cone OFF bipolar cells, giving a unique example of such a selective heritable retinal defect in humans. Furthermore, the authors provide the first clinical support for a new alternative role of VSX1 in cone biology, probably similar to that proposed for its goldfish ortholog during retinal differentiation.

Recurrence of keratoconus characteristics: a clinical and histologic follow-up analysis of donor grafts.

PURPOSE: To report on clinical corneal topography, histopathologic analysis, and fine structure findings in failed grafts after penetrating keratoplasty (PK) for keratoconus (KC). DESIGN: Retrospective, consecutive, interventional case series with histologic and clinical correlation. PARTICIPANTS: Twelve corneal buttons were obtained from consecutive patients undergoing repeated PK 10 to 28 years after the initial PK for KC. The indication for regrafting was endothelial deficiency in seven cases, irreversible immune graft rejection in two cases, and corneal ectasia in three cases. METHODS: Removed corneal buttons were examined by light and transmission electron microscopy. A potential correlation between the clinical and videokeratoscopic findings and the microscopic structural observations was analyzed. RESULTS: Preoperative simulated keratometry measured by TMS-1 (Tomey, New York, NY) or EyeSys CAS (EyeSys Technology, Houston, TX) ranged from 49.8 to 66.1 diopters. A pattern compatible with KC characteristics was observed in all cases. Fine structure analysis revealed Bowman's layer disruption or folds and stromal deposits in all corneal buttons. However, central corneal thinning was not present in any of the removed buttons. CONCLUSIONS: Structure changes compatible with the diagnosis of KC were observed in all donor buttons many years after PK on KC recipients. Recurrence of the KC characteristics may result from graft repopulation by recipients' keratocytes, aging of the grafted tissue, or both.