Role of Peoxisome Proliferator Activator Receptor γ on Blood Retinal Barrier Breakdown

The retinal vessels have two barriers: the retinal pigment epithelium and the retinal vascular endothelium. Each barrier exhibits increased permeability under various pathological conditions. This condition is referred to as blood retinal barrier (BRB) breakdown. Clinically, the most frequently encountered condition causing BRB breakdown is diabetic retinopathy. In recent studies, inflammation has been linked to BRB breakdown and vascular leakage in diabetic retinopathy. Biological support for the role of inflammation in early diabetes is the adhesion of leukocytes to the retinal vasculature (leukostasis) observed in diabetic retinopathy. PPARγ is a member of a ligand-activated nuclear receptor superfamily and plays a critical role in a variety of biological processes, including adipogenesis, glucose metabolism, angiogenesis, and inflammation. There is now strong experimental evidence to support the theory that PPARγ inhibits diabetes-induced retinal leukostasis and leakage, playing an important role in the pathogenesis of diabetic retinopathy. Therapeutic targeting of PPARγ may be beneficial to diabetic retinopathy

Evaluation of a partial retinal surface tear by optical coherence tomography

Differential diagnosis of retinal hemorrhage and partial tear of the retinal surface may be difficult in some cases. A 62-year-old woman was mistakenly followed-up for small retinal hemorrhages for more than 1 year. Blocked fluorescence specific to retinal hemorrhage was not observed by fluorescein angiography (FAG). Optical coherence tomography (OCT) clearly showed defects of the retinal surface indicating partial tears of the surface at the vitreo-retinal juncture and not hemorrhage. OCT is a useful and noninvasive device for the differential diagnosis of retinal hemorrhage and partial tear of the retinal surface

Gene Transfer Using Micellar Nanovectors Inhibits Choroidal Neovascularization In Vivo

PURPOSE: Age-related macular degeneration caused by choroidal neovascularization (CNV) remains difficult to be treated despite the recent advent of several treatment options. In this study, we investigated the in vivo angiogenic control by intravenous injection of polyion complex (PIC) micelle encapsulating plasmid DNA (pDNA) using a mice CNV model. METHODS: The transfection efficiency of the PIC micelle was investigated using the laser-induced CNV in eight-week-old male C57 BJ/6 mice. Firstly, each mouse received intravenous injection of micelle encapsulating pDNA of Yellow Fluorescent Protein (pYFP) on days 1,3 and 5. The expression of YFP was analyzed using fluorescein microscopy and western blotting analysis. In the next experiments, each mouse received intravenous injection of micelle encapsulating pDNA of soluble Fms-like tyrosine kinase-1 (psFlt-1) 1,3 and 5 days after the induction of CNV and the CNV lesion was analyzed by choroidal flatmounts on day 7. RESULTS: Fluorescein microscopy and western blotting analysis revealed that the expression of YFP was confirmed in the CNV area after injection of the PIC micelle, but the expression was not detected neither in mice that received naked pDNA nor those without CNV. Furthermore, the CNV area in the mice that received intravenous injection of the psFlt-1-encapsulated PIC micelle was significantly reduced by 65% compared to that in control mice (p<0.01). CONCLUSIONS: Transfection of sFlt-1 with the PIC micelle by intravenous injection to mice CNV models showed significant inhibition of CNV. The current results revealed the significant potential of nonviral gene therapy for regulation of CNV using the PIC micelle encapsulating pDNA

Quantitative Analysis of Cone Photoreceptor Distribution and Its Relationship with Axial Length, Age, and Early Age-Related Macular Degeneration

<div><p>Purpose</p><p>It has not been clarified whether early age-related macular degeneration (AMD) is associated with cone photoreceptor distribution. We used adaptive optics fundus camera to examine cone photoreceptors in the macular area of aged patients and quantitatively analyzed its relationship between the presence of early AMD and cone distribution.</p><p>Methods</p><p>Sixty cases aged 50 or older were studied. The eyes were examined with funduscopy and spectral-domain optical coherence tomography to exclude the eyes with any abnormalities at two sites of measurement, 2° superior and 5° temporal to the fovea. High-resolution retinal images with cone photoreceptor mosaic were obtained with adaptive optics fundus camera (rtx1, Imagine Eyes, France). After adjusting for axial length, cone packing density was calculated and the relationship with age, axial length, or severity of early AMD based on the age-related eye disease study (AREDS) classification was analyzed.</p><p>Results</p><p>Patient’s age ranged from 50 to 77, and axial length from 21.7 to 27.5 mm. Mean density in metric units and that in angular units were 24,900 cells/mm², 2,170 cells/deg² at 2° superior, and 18,500 cells/mm², 1,570 cels/deg² at 5° temporal, respectively. Axial length was significantly correlated with the density calculated in metric units, but not with that in angular units. Age was significantly correlated with the density both in metric and angular units at 2° superior. There was no significant difference in the density in metric and angular units between the eyes with AREDS category one and those with categories two or three.</p><p>Conclusion</p><p>Axial length and age were significantly correlated with parafoveal cone photoreceptor distribution. The results do not support that early AMD might influence cone photoreceptor density in the area without drusen or pigment abnormalities.</p></div

Early Stages of Age-Related Macular Degeneration: Racial/Ethnic Differences and Proposal of a New Classification Incorporating Emerging Concept of Choroidal Pathology

The progression of age-related macular degeneration (AMD) is determined by environmental and genetic factors, and phenotypic or molecular risk factors have been investigated extensively. Interestingly, risk factor profiles for advanced AMD differ among individuals, and one of the causes of variation may be explained by their ethnic background. Recent advances in retinal imaging technology have led to the identification of previously unrecognized risk factors for advanced AMD on optical coherence tomography (OCT) and OCT angiography, which expands the concept of traditional imaging risk factors such as drusen and pigmentary abnormalities visible on color fundus photographs. This OCT imaging modality has identified novel pathognomonic changes for early AMD, including the associated photoreceptor, retinal pigment epithelium, and underlying choroidal changes. Regarding features of multimodal imaging associated with the presence or progression of geographic atrophy, there is an international expert consensus classification system; however, features associated with the progression of macular neovascularization (MNV) are still obscure. To make a consensus towards understanding features associated with the risk of MNV, this review focuses on the early stages of AMD by summarizing imaging characteristics and early signs and classifications in view of advanced multimodal imaging technology. Recent evidence suggests that neovascular AMD is not a single disease entity but a heterogeneous disease characterized by MNV. Besides drusen, OCT features associated with pigment abnormalities, such as shallow irregular RPE elevation (SIRE, also known as double-layer sign), pachychoroid pigment epitheliopathy, and choriocapillaris ischemia, seem to confer a high risk of MNV developing, especially for Asian populations

Cone photoreceptor density in metric and angular units at 2° and 5° to the fovea.

<p>It was firstly automatically counted and then manually edited.</p

Identification of the sites for measurement in the images taken by adaptive optics fundus camera.

<p>Identification and measurement of cone distribution at 2° superior and 5° temporal to the fovea. Figures of a representative case are shown. Horizontal and vertical SD-OCT scan images centered on the fovea were obtained simultaneously with IR images using Spectralis (a). After the site corresponding to the fovea was identified on the IR image (orange cross in a) by referring to the OCT images, the sites at 2° superior and 5° temporal to the fovea on the IR image were located (yellow squares in a). Processed images from the adaptive optics (AO) fundus camera were overlaid with IR images by referring to retinal vessels in order to identify the sites of interest on AO images. A 60 pixel by 60 pixel square was placed at these sites (yellow square in b and c). Cone mosaic within the square was identified (red dots in the insets of 1b and 1c) and its distribution was assessed.</p