Day 2 :
University of Granada
Keynote: Glaucoma as a toll for hominid evolution: Constrains of the experimental animal models of glaucoma
Time : 09:00-09:25
Francisco Javier Carreras is a Tenured Professor of Ophthalmology, University of Granada. His research has pivoted around the pathogenesis of the glaucomas. He has contributed in the description and characterization of the Cameral Mucous Gel in humans. He has described a fluid conducting role for the perivascular glial sheat as well as the fenestrations of the basal lamina in the inner limiting membrane. His description of a pathogenetic role of the misdirection of aqueous humor flow is been incrementally delineated by his late contributions. He has developed a computational model of the optic pathways that helps to understand the structural/functional relationship in glaucoma.
Glaucoma continues to be a mysterious disease. High intraocular pressure (IOP), once the landmark of the disease, has been relegated to the humble role of risk factor, in spite of the fact that lowering IOP continues to be the only partially successful treatment. Even with a successfully controlled IOP to statistical standards, many patients still mysteriously progress in the loss of neural tissue. A novel pathogenetic mechanism has been recently suggested as the main agent of the disease. Under this new light, some structural details of the human eye, the result of the peculiar evolutionary development, gain an unexpected role in the presentation of the disease. As results of cladistic analysis, the human eye appears as particularly prone to suffer glaucoma as a consequence of the pursued evolutionary path. That makes glaucoma basically a human (and related hominid) scourge. Exclusive features of the human eye compared to other vertebrates involve both the anterior and posterior segment. Those features that facilitate glaucoma in humans are absent in many of the purported animal models for the disease, convoluting even more, for its inadequacy, the mystery of glaucoma. This suggests the division of the animal models into those that mimic the whole disease and those that only reproduce a pertinent histological feature. Unfortunately most animal models are based in high intraocular pressure which leaves out most cases of low or moderate pressure. For any animal model, it is important that the researcher establishes accurately the constraints of the model, to avoid jumping to conclusions.
Keynote: Aqueous humor fluid dynamics can be better understood by a real time perfusion system at constant pressure
Time : 09:25-09:50
Janardan Kumar is the Professor and Former Chair of Natural Sciences. He has earned MS in biochemistry from University of Allahabad and received PhD in chemistry at CDRI, Lucknow affiliated to Kanpur University in India. Being research Assistant Professor in the department of Cell Biology at Duke University in 1998, he developed his research interest to the field of glaucoma and joined the internationally renowned laboratory of Prof. David L Epstein at Duke Eye Center, Duke University, Durham, NC (USA). His work at Duke Eye Center provided opportunity to file two patents, one for glaucoma therapy and the other for vitrectomy. At TEI biosciences in 2002, he gained a unique experience on stem cell research. His strategies made him capable of inducing differentiation of insulin producing cells from adult human skin fibroblast stem cells using specific signaling complexes, and successful transplantation of these cells into three diabetic nude mice resulted of maintaining the normal glucose level for approximately a month.
For over half a century, glaucoma research has made little progress towards understanding the regulation of aqueous humor outflow resistance and fluid dynamics. Nevertheless, an understanding of the fluid dynamics in the eye, being either pulsatory or continuous as demonstrated in an ex vivo environment, would provide the key information as to the mechanisms of glaucoma. Without this understanding, it is difficult to predict definitively the role of outflow pathway cells in aqueous humor outflow resistance at the molecular level. Several designs of the perfusion systems have been proposed as measurements of the aqueous humor outflow facility in the enucleated eyes either at constant pressure or at constant flow. The major problem of perfusion systems measurement is that the equipment is not available commercially, so the perfusion equipment is self-assembled in laboratories after procuring the parts from different resources. Above all, the Grant perfusion system holds unique features that measure the outflow facility at constant pressure while two pairs of enucleated whole eyes are evaluated, simultaneously. Based on the same principle, the newly engineered real time perfusion system equipped with modern tools and technology using Balance Talk XL program 5.1 (Labtronics Inc., Canada) measures the outflow facility at constant pressure and was presented at ARVO 2006 by J Kumar. Clearly, the perfusion of H-7 in porcine eyes using the newly designed real time perfusion system model demonstrated that the perfusion of Optimedia, the composition similar to aqueous humor is a far superior physiological media than the traditionally used PBS plus glucose for the analysis of outflow facility. Our preliminary data analysis of outflow suggested that the aqueous outflow is discontinuous and exhibits a pulsatory motion. We anticipate that the newly designed real time perfusion system will be a valuable research tool for studies aimed at characterizing fluid dynamics as well as being easy to assemble and commercially available. If so, this will raise awareness for glaucoma research among basic scientists worldwide and contribute to a better understanding of aqueous flow and the mechanism of glaucoma leading to new treatment options.