Caveolar and non-Caveolar Caveolin-1 in ocular homeostasis and disease

Caveolae, specialized plasma membrane invaginations present in most cell types, play important roles in multiple cellular processes including cell signaling, lipid uptake and metabolism, endocytosis and mechanotransduction. They are found in almost all cell types but most abundant in endothelial cells, adipocytes and fibroblasts. Caveolin-1 (Cav1), the signature structural protein of caveolae was the first protein associated with caveolae, and in association with Cavin1/PTRF is required for caveolae formation. Genetic ablation of either Cav1 or Cavin1/PTRF downregulates expression of the other resulting in loss of caveolae. Studies using Cav1-deficient mouse models have implicated caveolae with human diseases such as cardiomyopathies, lipodystrophies, diabetes and muscular dystrophies. While caveolins and caveolae are extensively studied in extra-ocular settings, their contributions to ocular function and disease pathogenesis are just beginning to be appreciated. Several putative caveolin/caveolae functions are relevant to the eye and Cav1 is highly expressed in retinal vascular and choroidal endothelium, Müller glia, the retinal pigment epithelium (RPE), and the Schlemm's canal endothelium and trabecular meshwork cells. Variants at the CAV1/2 gene locus are associated with risk of primary open angle glaucoma and the high risk HTRA1 variant for age-related macular degeneration is thought to exert its effect through regulation of Cav1 expression. Caveolins also play important roles in modulating retinal neuroinflammation and blood retinal barrier permeability. In this article, we describe the current state of caveolin/caveolae research in the context of ocular function and pathophysiology. Finally, we discuss new evidence showing that retinal Cav1 exists and functions outside caveolae.     

Membrane-associated mucins of the ocular surface: New genes,new protein functions and new biological roles in human and mouse

The mucosal glycocalyx of the ocular surface constitutes the point of interaction between the tear film and the apical epithelial cells. Membrane-associated mucins (MAMs) are the defining molecules of the glycocalyx in all mucosal epithelia. Long recognized for their biophysical properties of hydration, lubrication, anti-adhesion and repulsion, MAMs maintain the wet ocular surface, lubricate the blink, stabilize the tear film and create a physical barrier to the outside world. However, it is increasingly appreciated that MAMs also function as cell surface receptors that transduce information from the outside to the inside of the cell. A number of excellent review articles have provided perspective on the field as it has progressed since 1987, when molecular cloning of the first MAM was reported. The current article provides an update for the ocular surface, placing it into the broad context of findings made in other organ systems, and including new genes, new protein functions and new biological roles. We discuss the epithelial tissue-equivalent with mucosal differentiation, the key model system making these advances possible. In addition, we make the first systematic comparison of MAMs in human and mouse, establishing the basis for using knockout mice for investigations with the complexity of an in vivo system. Lastly, we discuss findings from human genetics/genomics, which are providing clues to new MAM roles previously unimagined. Taken together, this information allows us to generate hypotheses for the next stage of investigation to expand our knowledge of MAM function in intracellular signaling and roles unique to the ocular surface.     

A multicenter report of the use of plasma rich in growth factors (PRGF) for the treatment of patients with ocular surface diseases in North America

PurposeTo investigate the efficacy and safety of plasma rich in growth factors (PRGF) eyedrops in the management of patients with ocular surface diseases in North America.MethodsMulticenter interventional case series of patients using PRGF eyedrops for the first time. A cohort of patients was analyzed for corneal staining score at initial visit and at 3 months of therapy with PRGF. Another cohort responded to a 10-item questionnaire that evaluated patients' satisfaction and safety, which included the symptom assessment questionnaire in dry eye (SANDE) score, after 6 months of PRGF treatment.ResultsA total of 153 patients were analyzed. Of these, 102 were reviewed for corneal epitheliopathy and 99 patients responded to the questionnaire. The mean (±SD) age of the population was 63.7 ± 17 years and 72.5% were female. The clinical indications for PRGF usage were dry eye (60%), neurotrophic keratopathy (15%), dormant corneal ulcers (12%), limbal stem cell deficiency (10%), and cicatrizing conjunctivitis (4%). At the final visit, 74.3% of patients showed an improvement of their corneal staining. Those who had punctate epithelial erosions or epithelial defects were reduced from 76.5% to 47% and 23.5% to 7.8% respectively (p < 0.0001). Symptoms, measured via SANDE score, significantly decreased from a median of 90 to 34.6 out of 100 points on follow-up (p < 0.0001). Only one patient (0.98%) complained of ocular burning sensation as a side effect.ConclusionsThis multicentric study demonstrates the safety and efficacy of the use of PRGF for treating signs and symptoms in patients with significant ocular surface diseases.