Müller cells are the major glia of the retina that serve numerous functions essential to retinal homeostasis, yet the contribution of Müller glial dysfunction to retinal diseases remains largely unknown. We have developed a transgenic model using a portion of the regulatory region of the retinaldehyde binding protein 1 gene for conditional Müller cell ablation and the consequences of primary Müller cell dysfunction have been studied in adult mice. We found that selective ablation of Müller cells led to photoreceptor apoptosis, vascular telangiectasis, blood-retinal barrier breakdown and, later, intraretinal neovascularization. These changes were accompanied by impaired retinal function and an imbalance between vascular endothelial growth factor-A (VEGF-A) and pigment epithelium derived factor. Intravitreal injection of cilliary neurotrophic factor inhibited photoreceptor injury but had no effect on the vasculopathy. Conversely, inhibition of VEGF-A activity attenuated vascular leak but did not protect photoreceptors. Our findings show that Müller glial deficiency may be an important upstream cause of retinal neuronal and vascular pathologies in retinal diseases. Combined neuroprotective and anti-angiogenic therapies may be required to treat Müller cell deficiency in retinal diseases and in other parts of the central nervous system associated with glial dysfunction.

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Abstract:The importance of scaffold biomaterials has been emphasized for in vitro culture of tissue-engineered cartilage in a three-dimensional (3D) environment. In this study, we examined the feasibility of fibrin glue, mixed with hyaluronic acid (HA) as a composite scaffold. Fibrin glue has been a useful cell delivery matrix for cartilage tissue engineering and HA is a key component of normal articular cartilage. Our hypothesis is that compared to fibrin itself, a fibrin/HA composite can have significantly enhanced properties, due mainly to the added benefits of HA in the matrix. Pieces of cartilage were isolated from rabbit knees and the chondrocytes were harvested through enzymatic digestion. Both fibrin and fibrin/HA composite were prepared and subsequently implanted in nude mice (n = 9, each group) for 1, 2, and 4 weeks, respectively. The retrieved specimens were then analyzed and the results were compared. Cartilage-like tissue formation was detected earlier with fibrin/HA specimens. They produced significantly higher amounts of the extracellular matrix (ECM) molecules, GAG, and collagen at each time point than those in fibrin. Interestingly, the fibrin/HA composite was also competent in maintaining its initial size. Histology-Safranin O/fast green and Alcian blue-of the retrieved specimens found more intense, uniform staining in the fibrin/HA composites. Analysis of the gene expression of the ECM molecules also confirmed the benefits of the composite with added HA in the maintenance of phenotypic stability. The present study suggests that fibrin/HA composite may serve as a dependable cell delivery vehicle as well as a structural basis for tissue-engineered cartilage. Key Words: Cartilage-Chondrocyte-Tissue engineering-Fibrin/hyaluronic acid composite-Fibrin.Biodegradable polymers have been one of the key components in cartilage tissue engineering. These polymers in the form of gel, sponge, and fiber serve as a scaffold in which chondrocytes are able to proliferate and differentiate. This technology allows cell/ polymer constructs to be implanted into cartilage defects and results in successful engraftment and new cartilage formation. General requirements of scaffolds are that they are 3D, highly porous with an interconnected pore network, biodegradable, and biocompatible. They should also carry appropriate surface properties for cell adhesion, proliferation, and differentiation. Proper mechanical properties are also required. Along with the synthetic scaffolds, many naturally derived scaffolds have been developed and examined in vitro and/or in vivo, including hyaluronate (HA) (1-3), fibrin (4-6), collagen (7), alginate (8,9), and chitosan (10). Although these materials have met those criteria in vitro, hyaline cartilage tissue formation is still challenging.It has been common practice that two or more biomaterials are combined to utilize the benefits of each biomaterial. Matrix engineering by adding various components has been successful to produce a composite matrix, such as fibrin-alginate (11), HAalg...

Retinal vascular diseases collectively represent a leading cause of blindness. Unsurprisingly, pathological characterisation and treatment of retinal 'vascular' diseases have primarily focused on the aetiology and consequences of vascular dysfunction. Far less research has addressed the contribution of neuronal and glial dysfunction to the disease process of retinal vascular disorders. Ample evidence now suggests that retinal vasculopathy only uncommonly occurs in isolation, usually existing in concert with neuropathy and gliopathy. Retinal glia (Müller cells, astrocytes and microglia) have been reported to exhibit morphological and functional changes in both early and advanced phases of almost every retinal vascular disease. It is anticipated that identifying the causes of glial activation and dysfunction, and their contribution to loss of vision in retinal vascular disease, will lead to a better understanding of retinal vascular diseases, which might ultimately be translated into novel clinical therapies.