In the anterior part of our eye there are two cavities filled with a watery but nutritive fluid called aqueous humor. One cavity, called the anterior chamber, lies just behind the cornea and in front of the iris. The other, called the posterior chamber, is a narrow space behind the iris and is surrounded by a mucsuloepithelial structure called the ciliary body. Aqueous humor is contiuously formed into the posterior chamber by the double layer ciliary epithelium that covers the ciliary body. Aqueous humor then sips through the hole at the center of iris, called the pupil, into the anterior chamber. Excess aqueous humor leaves the anterior chamber, by a pressure dependent way, mainly through a sieve-like structure called the trabecular meshwork located at the junction of the cornea and the sclera. Apart from supplying the nutrients and removing metabolic wastes from the avascular tissues of the eye, namely, the cornea, trabecular meshwork and the lens, the aqueous humor maintains the optimum intraocular pressure of~15 mmHg that are extremely important to maintain perfect geometry of the ocular structures necessary for optimum light transmission and good vision. An imbalance between the production of aqueous humor by the ciliary epithelium and its outflow through the trabecular meshwork can cause abnormally high intraocular pressure (above 20 mmHg), a painful condition called glaucoma. Abnormal high ocular pressure, if not treated, affect the posterior segment of the eye, particularly it causes the death or degeneration of the retinal ganglion cells, the cells that constitute our optic nerve and that are responsible to carry light signals from the photoreceptors to the brain to produce vision. If there is no healthy ganglion cell, there is no vision. Thus glaucoma is a blinding disease and it is the second most important eye disease responsible for vision loss throughout the world. Currently there is no cure to glaucoma and keeping the intraocular pressure under control is the only available and successful treatment to rescue the ganglion cells and to delay or stop vision loss. Intraocular pressure can be kept under control by either reducing the production of aqueous humoror by increasing its outflow. My research in the anterior segment of the eye is directed towards reducing the secretion/production of aqueous humor by the ciliary epithelium. To be able to reduce secretion, we must understand how this fluid is secreted by the ciliary epithelium. Currently the mechanisms and the molecular entities, i.e, the transporter proteins, channels and enzymes associated with the ciliary epithelium and that are responsible for shifting solutes and water from the blood to the posterior chamber in order to produce aqueous humor are not fully understood. Our laboratory is dedicated: (1) in identifying the transport molecules and enzymes required for aqueous humor secretion, (2) in characterizing these molecules functionally and (3) in identifying and characterizing the signal transduction mechanisms that regulate the functions of these molecules and (4) in pharmacological regulation of these molecules and /or the associated signal transduction mechanisms. My research in the posterior segment of the eye is directed toward finding the cause and understanding the mechanism of death of the ganglion cells in the retina. In glaucoma one of the initial phenotypic events in the death of ganglion cells appears to be the degeneration of the axons that collectively form the optic nerve. The axons of all the ganglion cells of the retina form a bundle at the exit point through the sclera, called the optic nerve head Retina is a complex nervous tissue and has many different cell types including the two most important supportive cells, the microglial cells and the astrocytes. Microglia and in particular the astrocytes have been associated with various aspects of glaucoma. These include biochemical and structural changes in the optic nerve head, biochemical changes in the extracellular matrix surrounding the optic nerve head, vascular pathology, and direct modulation of retinal ganglion cell survival. Our laboratory is dedicated: (1) in finding the biochemical and functional changes that occur in optic nerve head astrocytes in primary culture when subjected to high pressure, (2) in finding the biochemical changes that occur in the extracellular matrix, by analyzing the culture medium of astrocytes subjected to high pressure and (3) in identifying and characterizing the signal transduction mechanisms that underlie and regulate the above (1, 2) biochemical and functional changes. Experimental model systems and methodology we use We use novel, innovative and viable experimental model systems and up to date methodologies. Our laboratory is equipped with the state of the art facilities that are commensurate with cutting edge technology. Some of the experimental model systems we use are unique to this laboratory. For example, (1) the in vitro whole eye preparation to study physiology and pharmacology of aqueous humor dynamics, ocular vasculature, and ocular drug delivery, (2) primary culture of ocular nonpigmented cilliary epithelium to study ion transport mechanisms at the cellular and molecular level.
Mohammad Shahidullah, DVM, PhD
- Associate Research Professor
- Research Associate Professor, Ophthalmology
Shahidullah M, Mandal A, Delamere NA. "Activation of TRPV1 channels leads to stimulation of NKCC1 cotransport in the lens." Am. J. Physiol., Cell Physiol.. 2018. PMID: 30207782
Matagne V, Wondolowski J, Frerking M, et al. "Correcting deregulated Fxyd1 expression rescues deficits in neuronal arborization and potassium homeostasis in MeCP2 deficient male mice." Brain Res.. 2018;1697:45-52. PMID: 29902467