Breakthroughs

October 2003: How the Cornea Heals
Bascom Palmer Scientists Identify Novel Mechanisms with Implications for Improving Refractive Surgical Outcomes

The cornea is a key component of the eye’s optical system, enabling us to see clearly and sharply. To achieve these functions, the cornea must not only remain perfectly clear, it must also have exactly the right curvature.

A number of new surgical procedures have been developed to correct imperfect corneal curvature, with the goal of optimizing visual function. In the course of applying these procedures, surgeons have learned that the subsequent repair response can negatively affect the result, by compromising corneal clarity and destabilizing the correction in shape. In a paper published in the October 2003 issue of Investigative Ophthalmology and Visual Sciences, Bascom Palmer scientist M. Elizabeth Fini, Ph.D. and her team identify novel repair mechanisms in cornea that may be targeted in the design of new surgical and pharmacological measures to enhance surgical outcomes.

Repair in vascularized tissues such as skin is controlled primarily by platelets. These blood elements release repair-stimulating substances in the wound bed, in particular, a group of molecules called TGF-betas. Evidence indicates that these molecules are also active in corneal repair. However, unlike skin, the cornea contains no blood vessels and heals avascularly, thus the source of TGF-betas has been a mystery. That said, historic observation has suggested that the ocular surface tissue --- the epithelium --- functions as command central in corneal repair, substituting for platelets. Recent clinical observation backs up this idea and further suggests that the key to limiting the repair response is to reduce the potential for epithelial interaction with the underlying stromal tissue which is shaped in refractive surgical procedures.

Supporting the idea that repair-stimulating substances come from the epithelium, Fini and colleagues found that the repair response was inhibited if the epithelium was removed daily after surgery. The epithelium was determined to be a major source of TGF-beta, but in contrast to repair in skin, a form of TGF-beta called TGF-beta2 was the major repair-stimulating form. TGF-beta2 was confined to the epithelium of uninjured corneas or corneas undergoing simple re-epithelialization, a procedure in which the repair response is limited. However, TGF-beta2 was released into the corneal stroma following surgical procedures that penetrated through the epithelial basement membrane --- the thin layer of lining material underlying the epithelium --- and into the fibrous tissue of the corneal stroma. This suggested that the basement membrane directly controls release of TGF-beta2 from the epithelium. Following up in a number of different experiments, the researchers consistently obtained findings in support of this idea.

The overall implication of this work is that surgical procedures that limit damage to the epithelial basement membrane would also limit the repair response and lead to better surgical outcomes. Secondarily, the study suggests that molecules that are components of the basement membrane might be used therapeutically to inhibit the repair response. Finally, the results provide the rationale for specific targeting of TGF-beta2 over other TGF-betas, providing the opportunity for greater selectivity in pharmaceutical intervention.

Read more….
Click the link above to view the citation and scientific abstract for the above referenced article on the National Library of Medicine’s “PubMed” website. This also provides a link to the complete article published in the scientific journal, Investigative Ophthalmology and Visual Sciences.

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