Purpose To demonstrate the three-dimensional choroidal volume distribution in healthy subjects using enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT) and to evaluate its association with age, sex, and axial length. Design Retrospective case series. Participants One hundred and seventy six eyes from 114 subjects with no retinal or choroidal disease. Methods EDI SD-OCT imaging studies for healthy patients who had undergone a 31-raster scanning protocol on a commercial SD-OCT device were reviewed. Manual segmentation of the choroid was performed by two retinal specialists. Macular choroidal volume map and three-dimensional topography were automatically created by the built-in software of the device. Mean choroidal volume was calculated for each Early Treatment Diabetic Retinopathy Study (ETDRS) subfield. Regression analyses were used to evaluate the correlation between macular choroidal volume and age, sex, and axial length. Main Outcome Measures Three-dimensional topography and ETDRS-style volume map of the choroid. Results Three-dimensional topography of the choroid and volume map was obtained in all cases. The mean choroidal volume was 0.228 ± 0.077 mm3 for the center ring and 7.374 ± 2.181 mm3 for the total ETDRS grid. The nasal quadrant showed the lowest choroidal volume, and the superior quadrant the highest. The temporal and inferior quadrants did not show different choroidal volume values. Choroidal volume in all the EDTRS rings was significantly correlated with axial length after adjustment for age (P<0.0001), with age after adjustment for axial length (P<0.0001) and with sex after adjustment for axial length (P<0.05). Choroidal volume decreases by 0.54 mm3 (7.32%) for every decade and by 0.56 mm3 (7.59%) for every mm of axial length. Males have a 7.37% greater choroidal volume compared to that of females. Conclusions EDI SD-OCT is non-invasive and well-tolerated procedure with an excellent ability to visualize three-dimensional topography of the choroid and to measure choroidal volume at the posterior pole using manual segmentation. Age and axial length are inversely correlated with choroidal volume, most likely leading to changes in retinal metabolic support in old and high myopic patients. Sexual differences should be considered when interpreting an EDI SD-OCT scan of the choroid.

The rs1061170T/C variant encoding the Y402H change in complement factor H (CFH) has been identified by genome-wide association studies as being significantly associated with age-related macular degeneration (AMD). However, the precise mechanism by which this CFH variant impacts the risk of AMD remains largely unknown. Oxidative stress plays an important role in many aging diseases, including cardiovascular disease and AMD. A large amount of oxidized phospholipids (oxPLs) are generated in the eye because of sunlight exposure and high oxygen content. OxPLs bind to the retinal pigment epithelium and macrophages and strongly activate downstream inflammatory cascades. We hypothesize that CFH may impact the risk of AMD by modulating oxidative stress. Here we demonstrate that CFH binds to oxPLs. The CFH 402Y variant of the protective rs1061170 genotype binds oxPLs with a higher affinity and exhibits a stronger inhibitory effect on the binding of oxPLs to retinal pigment epithelium and macrophages. In addition, plasma from non-AMD subjects with the protective genotype has a lower level of systemic oxidative stress measured by oxPLs per apolipoprotein B (oxPLs/apoB). We also show that oxPL stimulation increases expression of genes involved in macrophage infiltration, inflammation, and neovascularization in the eye. OxPLs colocalize with CFH in drusen in the human AMD eye. Subretinal injection of oxPLs induces choroidal neovascularization in mice. In addition, we show that the CFH risk allele confers higher complement activation and cell lysis activity. Together, these findings suggest that CFH influences AMD risk by modulating oxidative stress, inflammation, and abnormal angiogenesis.

Abstract-The fruit fly, Drosophila melanogaster, has served as a valuable model/organism for the study of aging and was the first organism possessing a circulatory system to have its genome completely sequenced. However, little is known about the function of the heartlike organ of flies during the aging process. We have developed methods for studying cardiac function in vivo in adult flies. Using 2 different cardiovascular stress methods (elevated ambient temperature and external electrical pacing), we found that maximal heart rate is significantly and reproducibly reduced with aging in Drosophila, analogous to observations in elderly humans. We also describe for the first time several other aspects of the cardiac physiology of young adult and aging Drosophila, including an age-associated increase in rhythm disturbances. These observations suggest that the study of declining cardiac function in aging flies may serve as a genetically tractable model for genome-wide mutational screening for genes that participate in or protect against cardiac aging and disease.

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