Superoxide Production and Functions in Corneal Cells

Medical College Of Wisconsin, Milwaukee WI

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Linked publications & trials

Abstract

The cornea provides the majority of the refractive power required to focus the incoming light on the retina[unreadable] and functions as a barrier protecting the eye from the environment. The cornea must maintain the proper[unreadable] radius of curvature and clarity to function properly. Preserving these properties is not an easy task because[unreadable] the cornea is exposed to the environment and as such it is subject to abrasions, infections and ultraviolet[unreadable] light. Due to the fact that the cornea is the principal source of refractive power it is subjected to surgical[unreadable] procedures to improve or restore vision. All of these factors are capable of causing inflammation resulting in[unreadable] either transient or permanent corneal edema or scarring that compromise the ability to see clearly. Corneal[unreadable] diseases and injuries are the leading cause of visits to eye care clinicians and have compromised the vision[unreadable] of more than 250 million people worldwide, leading to blindness in over 6 million. The goal of this grant is to[unreadable] characterize a newly identified group of proteins that are responsible for the production of superoxide by[unreadable] corneal cells. Superoxide is one of a group of molecules referred to as reactive oxygen species (ROS).[unreadable] These molecules not only exert oxidative stress on tissues but also regulate normal cellular functions. The[unreadable] aims of this grant focus on the mechanisms by which corneal cells generate superoxide and the[unreadable] mechanism(s) through which it affects the functions of corneal stromal cells. We will examine the proteins[unreadable] composing a newly discovered protein complex in corneal cells called NADPH oxidase. Knowledge of the[unreadable] structure of the proteins of the complex is a key to understanding how to regulate its activities. We will[unreadable] determine the cellular location and the contribution of the complex to total cellular production of superoxide.[unreadable] The second aim will investigate how the activity of the NADPH oxidase is regulated. Regulation of the activity[unreadable] of the complex in critical because over production of superoxide can be detrimental to cells but cell survival[unreadable] may be compromised if to little is produced. The third aim will determine how superoxide regulates cell[unreadable] survival. Survival of all the corneal cell types is critical to maintaining corneal function. We believe that[unreadable] superoxide plays a critical role in the mechanism(s) by which growth factors and cytokines influence corneal[unreadable] cells. Completing the aims of this grant will provide insight required to develop new drugs to regulate[unreadable] superoxide production and maintain the corneal function following infection, injury or surgery.[unreadable] [unreadable]