EXROP Projects: Simon W. M. John

Simon W. M. John
Summer Lab Size: 12
Local Summer Program: Summer Student Program
Program Dates: May 26-August 12, 2013

Identifying Genes Controlling Aqueous Humor Outflow Using Cutting Edge Techniques

Elevated intraocular pressure (IOP) is a key causal risk factor for the blinding disease glaucoma, which will afflict 80 million people by 2020. Elevated IOP arises from increased resistance to drainage of the aqueous humor (AQH). The AQH drains through two routes. The conventional pathway is through the trabecular meshwork (TM) followed by Schlemm’s Canal (SC) — both located in the wall of the iridocorneal angle at the limbus. The conventional pathway drains the majority of the AQH and the amount of drainage through it is pressure dependent. In normal individuals, IOP is maintained within a narrow range, indicating a high degree of regulation. The mechanisms controlling AQH outflow and hence IOP are unclear. We are actively engaged in determining the molecular basis of the mechanisms controlling AQH outflow and IOP. To complete this study effectively we need to develop modern tools to conditionally knock out genes using Cre-LoxP technology. Towards this effort, one project that we are focusing on is to identify genes that are exclusively expressed in either the SC or TM using immunofluorescence, in situ hybridization, and mouse strains expressing fluorescent proteins in the SC or TM. The goal, after gene identification, is to express Cre-recombinase under control of the promoter of genes identified. Another project will involve screening chemical compounds for their effect on AQH outflow, which will be measured using a device that we have developed in our lab. In the Simon John lab you will have the opportunity to learn a wide array of techniques including mouse genetics, physiological measurements of IOP and AQH outflow, high-resolution light microscopy and electron microscopy, and next generation sequencing. You will work in a scientific environment that is both intense and exciting.

Alleviating the Neuronal Energy Crisis in Glaucoma Using Gene Therapy

Retinal ganglion cell axons in the optic nerve head are insulted early in animal models of glaucoma. Recent analysis suggests a neuronal energy crisis in retinal ganglion cells that may contribute to or drive cell death, optic nerve degeneration, and vision loss. The John lab will be using cutting-edge gene therapy in DBA/2J mice (model of age-related ocular hypertensive glaucoma) to test our energy crisis related hypotheses.

Scientist Profile

Investigator
The Jackson Laboratory
Genetics, Neuroscience