The objective of this study is to understand the pathogenesis of corneal edema which occurs, in some patients, following intraocular surgery. At greatest risk are diabetic patients, patients with guttata, maltino implant patients and possibly long-term contact lens wearers, all of whom have severe endothelial polymegathism, particularly as they approach the age for cataract surgery. Our basic premise is that the cornea of these patients have a compromised endothelium and additional stress such as intraocular surgery, postoperative inflammation and increases in intraocular pressure will affect the metabolic pump and barrier functions of the compromised endothelium resulting in postoperative corneal edema. The proposed studies should further our understanding of the pathogenesis of corneal edema and the prevention of postsurgical corneal edema. We propose to test the following hypothesis about the specific effects of each of three factors on the compromised corneal endothelium. (1) that the corneal endothelium has a regeneration zone (stem cells) that maintains a constant supply of new cells to enable endothelial cell migration from the peripheral limbal region to the central region of the cornea: these studies will evaluate endothelial cells that are transit amphifying cells, terminally differential cells, the effect of mitomycin C, glaucoma drainage implants and polymegathism on the endothelial cell population in the three zones of endothelial cells: regenerative, storage and migration. (2) that glutathoine will protect corneal endothelial cells against apoptosis and that the cellular levels of reduced glutathione (GSH) will modulate Fas-mediated apoptosis. And (3) that endotoxin (LPS) produced during inflammation in the presence of the binding protein (LPB) and the anchoring glycoprotein CD-14 causes the release of cytokines from the corneal endothelial cells which can result in corneal edema. The results of these studies should provide a better understanding of the corneal endothelial response following intraocular surgery and in the prevention of postoperative corneal edema that can occur in stressed corneas with low cell numbers and following gram negative intraocular inflammation.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY000933-35
Application #
7057241
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Shen, Grace L
Project Start
1989-07-01
Project End
2008-04-30
Budget Start
2006-05-01
Budget End
2008-04-30
Support Year
35
Fiscal Year
2006
Total Cost
$296,856
Indirect Cost
Name
Emory University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
FourniƩ, Pierre R; Gordon, Gabriel M; Dawson, Daniel G et al. (2010) Correlation between epithelial ingrowth and basement membrane remodeling in human corneas after laser-assisted in situ keratomileusis. Arch Ophthalmol 128:426-36
Edelhauser, Henry F; Boatright, Jeffrey H; Nickerson, John M et al. (2008) Drug delivery to posterior intraocular tissues: third Annual ARVO/Pfizer Ophthalmics Research Institute Conference. Invest Ophthalmol Vis Sci 49:4712-20
Ghate, Deepta A; Holley, Glenn; Dollinger, Harli et al. (2008) Evaluation of endothelial mucin layer thickness after phacoemulsification with next generation ophthalmic irrigating solution. Cornea 27:1050-6
Shanyfelt, Leia M; Dickrell, Pamela L; Edelhauser, Henry F et al. (2008) Effects of laser repetition rate on corneal tissue ablation for 193-nm excimer laser light. Lasers Surg Med 40:483-93
Randleman, J Bradley; Dawson, Daniel G; Grossniklaus, Hans E et al. (2008) Depth-dependent cohesive tensile strength in human donor corneas: implications for refractive surgery. J Refract Surg 24:S85-9
Dawson, Daniel G; Randleman, J Bradley; Grossniklaus, Hans E et al. (2008) Corneal ectasia after excimer laser keratorefractive surgery: histopathology, ultrastructure, and pathophysiology. Ophthalmology 115:2181-2191.e1
Fournie, Pierre R; Gordon, Gabriel M; Dawson, Daniel G et al. (2008) Correlations of long-term matrix metalloproteinase localization in human corneas after successful laser-assisted in situ keratomileusis with minor complications at the flap margin. Arch Ophthalmol 126:162-70
McCarey, Bernard E; Edelhauser, Henry F; Lynn, Michael J (2008) Review of corneal endothelial specular microscopy for FDA clinical trials of refractive procedures, surgical devices, and new intraocular drugs and solutions. Cornea 27:1-16
Dawson, Daniel G; Grossniklaus, Hans E; McCarey, Bernard E et al. (2008) Biomechanical and wound healing characteristics of corneas after excimer laser keratorefractive surgery: is there a difference between advanced surface ablation and sub-Bowman's keratomileusis? J Refract Surg 24:S90-6
Dawson, Daniel G; Schmack, Ingo; Holley, Glenn P et al. (2007) Interface fluid syndrome in human eye bank corneas after LASIK: causes and pathogenesis. Ophthalmology 114:1848-59

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