Age-related macular degeneration (AMD) is a late-onset, multifactorial, neurodegenerative disease of the retina and the leading cause of irreversible vision loss in the elderly in the Western world. We describe here a murine model that combines three known AMD risk factors: advanced age, high fat cholesterol-rich (HF-C) diet, and apolipoprotein E (apoE) genotype. Eyes of aged, targeted replacement mice expressing human apoE2, apoE3, or apoE4 and maintained on a HF-C diet show apoE isoform-dependent pathologies of differential severity. ApoE4 mice are the most severely affected. They develop a constellation of changes that mimic the pathology associated with human AMD. These alterations include diffuse sub-retinal pigment epithelial deposits, drusenoid deposits, thickened Bruch's membrane, and atrophy, hypopigmentation, and hyperpigmentation of the retinal pigment epithelium. In extreme cases, apoE4 mice also develop marked choroidal neovascularization, a hallmark of exudative AMD. Neither age nor HF-C diet alone is sufficient to elicit these changes. We document choroidal neovascularization and other AMD-like ocular pathologies in an animal model that exploits known AMD risk factors. The model is additionally attractive because it is not complicated by invasive experimental intervention. Our findings in this model implicate the human apoE E4 allele as a susceptibility gene for AMD and support the hypothesis that common pathogenic mechanisms may underlie AMD and Alzheimer's disease.amyloid ͉ choroidal neovascularization ͉ macula ͉ retinal pigment epithelium ͉ cholesterol A ge-related macular degeneration (AMD) is the leading cause of irreversible vision loss in people over the age of 65, accounting for the majority of registered blindness in Western Europe and North America (1). A family of disorders, AMD is characterized by progressive loss of central, high-acuity vision due to dysfunction and death of photoreceptors (PRs) in the center of the retina, the macula. AMD pathology also impacts the retinal pigment epithelium (RPE, the cells responsible for support of PRs and maintenance of the choroidal blood-eye barrier), the choriocapillaris (CC, the primary capillary bed of the choroid), and Bruch's membrane (BrM, a stratified extracellular matrix between the RPE and the CC). Early AMD is characterized by moderate vision loss associated with characteristic extracellular lesions that form between the RPE and BrM. These lesions can be focal (drusen) or diffuse (basal deposits) (2-4). Late AMD is subdivided into two forms, dry or wet. Dry (geographic atrophy) is characterized by PR loss causing severe visual impairment concomitant with extensive RPE atrophy, whereas wet (exudative) features the sequela of choroidal neovascularization (CNV, i.e., in growth of the CC through BrM and under the RPE in the plane of drusen and basal deposits) (5).AMD is a complex disease in which the contributions of many genetic and environmental factors are confounding. The strongest known risk factor for AMD is advanced age, with the ri...

A high resolution urban thermal sharpener (HUTS) was developed that increases the resolution of thermal infrared (TIR) data to that of visible and near infrared (VNIR) data by fitting the relationship between radiometric surface temperature, normalized difference vegetation index (NDVI) and surface albedo (α). HUTS was applied to TIR data aggregated to 90 m to represent a satellite acquired dataset and validated against the measured 10 m data from aircraft over San Juan, Puerto Rico. HUTS sharpening reduced the root mean square error of surface temperature at the high resolution by 17 % compared to no sharpening and outperformed other sharpening methods. HUTS is proposed as a useful tool to study urban meteorology and climatology at the microscale using ASTER satellite data.

gamma-Aminobutyric acid (GABA) plasma membrane transporters (GATs) influence synaptic neurotransmission by high-affinity uptake and release of GABA. The distribution and cellular localization of GAT-1, GAT-2, and GAT-3 in the rat retina have been evaluated by using affinity-purified polyclonal antibodies directed to the C terminus of each of these GAT subtypes. Small GAT-1-immunoreactive cell bodies were located in the proximal inner nuclear layer (INL) and ganglion cell layer (GCL), and processes were distributed to all laminae of the interplexiform layer (IPL). Varicose processes were in the optic fiber layer (OFL) and the outer plexiform layer (OPL). Weak GAT-1 immunostaining surrounded cells in the INL and GCL, and it was found in the OFL and OPL and in numerous processes in the outer nuclear layer (ONL) that ended at the outer limiting membrane. GAT-1 is therefore strongly expressed by amacrine, displaced amacrine, and interplexiform cells and weakly expressed by Müller cells. GAT-2 immunostaining was observed in the retina pigment epithelium and the nonpigmented ciliary epithelium. GAT-3 immunoreactivity was distributed to the OFL, to all laminae of the IPL, GCL and INL, and to processes in the ONL that ended at the outer limiting membrane. Small GAT-3-immunoreactive cell bodies were in the proximal INL and GCL. GAT-3 is therefore strongly expressed by Müller cells, and by some amacrine and displaced amacrine cells. Together, these observations demonstrate a heterologous distribution of GATs in the retina. These transporters are likely to take up GABA from, and perhaps release GABA into, the synaptic cleft and extracellular space. This suggests that GATs regulate GABA levels in these areas and thus influence synaptic neurotransmission.