Macular Degeneration: Schaal S

Schaal S, Tezel TH, Kaplan HJ. · No affiliation provided · Ocul Immunol Inflamm. · Pubmed #19065414 No free full text.

This publication has no abstract.

Tezel TH, Geng L, Lato EB, Schaal S, Liu Y, Dean D, Klein JB, Kaplan HJ. · Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA. · Invest Ophthalmol Vis Sci. · Pubmed #19060278 No free full text.

Abstract: PURPOSE: To demonstrate the production of hemoglobin by human retinal pigment epithelium (RPE). METHODS: Proteomic analysis using 10 donor eyes identified hemoglobin as a major constituent of soluble human RPE proteome. Western blot analysis, RT-PCR, and immunocytochemistry were used to confirm the RESULTS: The presence of erythrocyte-specific proteins within primary human RPE cytosol was investigated to rule out phagocytosis as the source of hemoglobin. ELISA was used to determine the rate of hemoglobin secretion from human RPE cells. Globin mRNA expression of human RPE was studied in comparison with a human erythroblast cell line and a spontaneously transformed human RPE cell line (ARPE-19). results. Hemoglobin is a regular constituent of soluble human RPE proteome. RT-PCR and Western blot analysis confirmed the presence of hemoglobin in human RPE. No other erythrocyte-specific proteins were detected within human RPE cytosol. Hemoglobin expression persisted up to seven passages in vitro. Human RPE globin expression exceeded that in human erythroblast and ARPE-19 cells. Immunohistochemistry revealed the presence of hemoglobin within RPE and Bruch's membrane. The hemoglobin release rate was calculated to be 1.9+/-1.2 attomoles per cell per hour. CONCLUSIONS: Hemoglobin expression by human RPE brings a new perspective to the understanding of oxygen transport to the outer retina. Malfunction of RPE-hemoglobin production may underlie the pathophysiology of ocular diseases characterized by subfoveal hypoxia and VEGF upregulation, such as age-related macular degeneration and diabetic retinopathy. Pharmacologic modulations of local hemoglobin production in RPE cells will create new opportunities to interfere with the course of these diseases.

Schaal S, Kaplan HJ, Tezel TH. · Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA. · Ophthalmology. · Pubmed #18930553 No free full text.

Abstract: PURPOSE: To determine whether repetitive injections of intravitreal bevacizumab and/or triamcinolone acetate in patients with exudative age-related macular degeneration (AMD) results in a decrease in biological response. DESIGN: Retrospective comparative case series. PARTICIPANTS: Forty-three eyes of 43 patients with exudative AMD. METHODS: Pre- and postinjection optical coherence tomography (OCT) sections of 43 patients with AMD were analyzed to determine the change in the biologic response after each subsequent injection of intravitreal bevacizumab (2.5 mg/100 microL), preservative-free triamcinolone acetonide (pfTA) (4.0 mg/100 microL), or a combination of bevacizumab (1.25 mg/50 microL) and pfTA (2.0 mg/50 microL). The retinal thickness of each OCT sector was determined and expressed as volume. Standardized volumetric change index (SVCI) was determined to identify a statistically significant change. Pre- and postinjection (6 weeks) SVCI differences were plotted as a function of time to determine the biological response after each intravitreal treatment. MAIN OUTCOME MEASURES: Change in SVCI after intravitreal injections and the number of injections required to decrease the biological response by 50% (INJ(50)). RESULTS: There was no difference in the age, gender, and preinjection thickness of the retina in each of the 3 groups. The SVCI after intravitreal bevacizumab injections decreased, indicating a possible tachyphylactic response to bevacizumab. This decrease in biological response was partially alleviated with the addition of pfTA. Combination of pfTA and bevacizumab increased the INJ(50) from 2.9 with bevacizumab alone to 5.1 injections. A biphasic biologic response was observed with pfTA characterized by a rapid increase in efficacy with the second injection, peaking at the third injection and gradually decreasing afterward. CONCLUSIONS: Repeated intravitreal injections of bevacizumab in exudative AMD seemed to be associated with decreased bioefficacy. However, combined pharmacotherapy with triamcinolone acetate lessened this effect. Thus, multitargeted pharmacotherapy in exudative AMD may have a therapeutic benefit. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.