A complement factor H homolog, heparan sulfation, and syndecan maintain inversin compartment boundaries in cilia.

Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly. Canonical disease models suggest that defective interactions between complement factor H (CFH) and cell surface heparan sulfate (HS) result in increased alternative complement pathway activity, cytolytic damage, and tissue inflammation in the retina. Although these factors are thought to contribute to increased disease risk, multiple studies indicate that noncanonical mechanisms that result from defective CFH and HS interaction may contribute to the progression of AMD as well.

Effects of aging and environmental tobacco smoke exposure on ocular and plasma circulatory microRNAs in the Rhesus macaque.

Purpose: To identify changes induced by environmental tobacco smoke (ETS) in circulatory microRNA (miRNA) in plasma and ocular fluids of the Rhesus macaque and compare these changes to normal age-related changes. Tobacco smoke has been identified as the leading environmental risk factor for age-related macular degeneration (AMD).

Methods: All Rhesus macaques were housed at the California National Primate Research Center (CNPRC), University of California, Davis.

Protective Effect of Intravitreal Administration of Exosomes Derived from Mesenchymal Stem Cells on Retinal Ischemia.

Purpose: Exosomes derived from human mesenchymal stem cells (hMSCs) cultured under hypoxic conditions contain proteins and growth factors that promote angiogenesis. This study investigated the effect of intravitreal administration of these exosomes on retinal ischemia using a murine model.

Methods: Oxygen-induced retinopathy (OIR) was induced by exposing one-week-old male C57BL/6J mice to 5 days of 75% hyperoxic conditioning, and returning to room air.

Effect of Uveal Melanocytes on Choroidal Morphology in Rhesus Macaques and Humans on Enhanced-Depth Imaging Optical Coherence Tomography.

Purpose: To compare cross-sectional choroidal morphology in rhesus macaque and human eyes using enhanced-depth imaging optical coherence tomography (EDI-OCT) and histologic analysis.

Methods: Enhanced-depth imaging-OCT images from 25 rhesus macaque and 30 human eyes were evaluated for choriocapillaris and choroidal-scleral junction (CSJ) visibility in the central macula based on OCT reflectivity profiles, and compared with age-matched histologic sections. Semiautomated segmentation of the choriocapillaris and CSJ was used to measure choriocapillary and choroidal thickness, respectively.

Intravitreal Administration of Human Bone Marrow CD34+ Stem Cells in a Murine Model of Retinal Degeneration.

Purpose: Intravitreal murine lineage-negative bone marrow (BM) hematopoietic cells slow down retinal degeneration. Because human BM CD34+ hematopoietic cells are not precisely comparable to murine cells, this study examined the effect of intravitreal human BM CD34+ cells on the degenerating retina using a murine model.

Methods: C3H/HeJrd1/rd1 mice, immunosuppressed systemically with tacrolimus and rapamycin, were injected intravitreally with PBS (n = 16) or CD34+ cells (n = 16) isolated from human BM using a magnetic cell sorter and labeled with enhanced green fluorescent protein (EGFP).

Localization of complement factor H gene expression and protein distribution in the mouse outer retina.

Purpose: To determine the localization of complement factor H (Cfh) mRNA and its protein in the mouse outer retina.

Methods: Quantitative real-time PCR (qPCR) was used to determine the expression of Cfh and Cfh-related (Cfhr) transcripts in the RPE/choroid. In situ hybridization (ISH) was performed using the novel RNAscope 2.

Age-dependent increase in miRNA-34a expression in the posterior pole of the mouse eye.

Purpose: MicroRNA-34a (miR-34a) has been implicated in neurodegeneration. MiR-34a belongs to a signaling network involving p53 and Sirt-1. This network responds to DNA damage with further downstream signals that induce senescence or apoptosis.

A strong genetic determinant of hyperoxia-related retinal degeneration on mouse chromosome 6.

Purpose: Hyperoxia-related retinal degeneration (HRRD) is a model system in the mouse in which elevated oxygen levels are used to induce retinal degeneration. The hypothesis for the present study was that strain differences in HRRD susceptibility are due to allelic variants of one or more genes in the mouse genome whose human orthologues should be important targets for research and drug development.

Methods: C57BL/6J, A/J, or B.

Regulation of cysteine cathepsin expression by oxidative stress in the retinal pigment epithelium/choroid of the mouse.

Cystatin C is the major inhibitor of the cysteine cathepsins. Polymorphisms in the cystatin C gene have recently been associated with the risk of developing Age-related Macular Degeneration (AMD). Oxidative stress is also thought to play a key role in the pathogenesis of AMD.

Changes in the spatial expression of genes with aging in the mouse RPE/choroid.

Purpose: We recently used microarray and reverse transcriptase PCR (RT-PCR) analysis to show an upregulation of cathepsin S (CatS) and glutathione peroxidase 3 (GPX3) in the aging mouse RPE/choroid. To evaluate the mRNA distribution and levels in the RPE and choroid, in situ hybridizations were performed.

Methods: Eye sections from 2-month-old and 24-month-old C57BL/6 mice were probed for CatS or GPX3 mRNA by in situ hybridization.