PURPOSE-To examine changes of select reduction-oxidation (redox) sensitive proteins from human donor retinal pigment epithelium (RPE) at four stages of age-related macular degeneration (AMD). DESIGN-Experimental study.METHODS-Human donor eyes were obtained from the Minnesota Lions Eye Bank and graded using the Minnesota Grading System (MGS) into four stages that correspond to stages defined by the age-related eye disease study (AREDS). Protein content in RPE homogenates was measured using Western immunoblotting with protein-specific antibodies.RESULTS-The content of several antioxidant enzymes and specific proteins that facilitate refolding or degradation of oxidatively damaged proteins increased significantly in MGS stage 3. These proteins are involved in the primary (copper-zinc superoxide dismutase [CuZnSOD], manganese superoxide dismutase [MnSOD], and catalase) and secondary (heat shock protein [HSP] 27, HSP 90, and proteasome) defense against oxidative damage. Additionally, the insulin prosurvival receptor exhibited disease-related upregulation.CONCLUSIONS-The pattern of protein changes identified in human donor tissue graded using the MGS support the role of oxidative mechanisms in the pathogenesis and progression of AMD. The MGS uses nearly identical clinical definitions and grading criteria of AMD that are used in the AREDS, so our results apply to clinical and epidemiologic studies using similar definitions. Results from our protein analysis of human donor tissue helps to explain altered oxidative stress regulation and cell-survival pathways that occur in progressive stages of AMD.Age-related macular degeneration (amd) is the leading cause of blindness in developed countries 1-9 . The number of affected individuals in the United States alone is expected to increase nearly twofold, to approximately three million by the year 2020. 10 Fortunately, therapeutic options are improving. The use of antioxidant vitamins has been shown to delay disease progression at an intermediate stage, 11 and rapid innovation in the use of antiangiogenic therapies has resulted in new clinical methods to treat the exudative phase of AMD. 12-18 However, developing new treatment and prevention strategies targeting earlier stages of the disease requires a better understanding of the underlying disease mechanisms.Findings from the Age-Related Eye Disease Study (AREDS) clearly support the hypothesis that oxidative mechanisms play a significant role in the progression of AMD. Although several studies have shown that the intake of antioxidant-rich foods lowers the risk of AMD, 19-24 others have not supported this conclusion. 25-27 Cigarette smoking, a pro-oxidant, NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript significantly increases the risk of AMD, and this association is well supported in numerous, well-designed studies. 28-35The retinal pigment epithelium (RPE) is subject to a particularly high level of oxidative stress because of locally elevated oxygen tension, high polyunsaturated lipid con...

Operative treatment of perianal fistulas in patients with Crohn's disease resulted in complete healing in approximately 60 percent of patients. Preoperative infliximab infusion did not affect overall healing rates.

Aims/hypothesis Diabetic retinopathy is the most common complication of diabetes and a leading cause of blindness among working-age adults. Anatomical and functional changes occur in the retina and retinal pigment epithelium (RPE) prior to clinical symptoms of the disease. However, the molecular mechanisms responsible for these early changes, particularly in the RPE, remain unclear. To begin defining the molecular changes associated with pre-retinopathic diabetes, we conducted a comparative proteomics study of human donor RPE. Methods The RPE was dissected from diabetic human donor eyes with no clinically apparent diabetic retinopathy (n=6) and from eyes of age-matched control donors (n= 17). Soluble proteins were separated based upon their mass and charge using two-dimensional (2-D) gel electrophoresis. Protein spots were visualised with a fluorescent dye and spot densities were compared between diabetic and control gels. Proteins from spots with significant disease-related changes in density were identified using mass spectrometry.Results Analysis of 325 spots on 2-D gels identified 31 spots that were either up-or downregulated relative to those from age-matched control donors. The protein identity of 18 spots was determined by mass spectrometry. A majority of altered proteins belonged to two major functional groups, metabolism and chaperones, while other affected categories included protein degradation, synthesis and transport, oxidoreductases, cytoskeletal structure and retinoid metabolism. Conclusions/interpretation Changes identified in the RPE proteome of pre-retinopathic diabetic donor eyes compared with age-matched controls suggest specific cellular alterations that may contribute to diabetic retinopathy. Defining the pre-retinopathic changes affecting the RPE could provide important insight into the molecular events that lead to this disease.

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Purpose: To retrospectively report the outcomes of patients presenting to our facility with central retinal artery occlusion and receiving therapy with hyperbaric oxygen (HBO).Methods: This was a retrospective, chart review at a single hospital center. Patients with diagnosed central retinal artery occlusion were treated with HBO twice daily for 5 days during their inpatient stay for a total of 10 HBO treatments. Main outcome was change from the documented presenting best-corrected visual acuity to discharge best-corrected visual acuity. Thirty-nine patients with central retinal artery occlusion were included in the analysis during a 30-month period.Results: Twenty-eight of 39 patients (72%) had some improvement in acuity. There was a mean of 5.05 lines of improvement using a modified Snellen chart after completing their HBO treatment course. Patients treated within 12 hours of symptom onset showed the greatest improvement in their visual acuity (6.11 mean lines of improvement). Complications of therapy included middle ear barotrauma (10/39) and confinement anxiety (1/39) and did not interfere with the therapy regimen or hospital course.Conclusion: This retrospective case series supports the use of emergent HBO therapy as a viable treatment option for patients with central retinal artery occlusion. Hyperbaric oxygen therapy was safely administered and well tolerated.