Histological Characterization of the Dicer1 Mutant Zebrafish Retina.

DICER1, a multidomain RNase III endoribonuclease, plays a critical role in microRNA (miRNA) and RNA-interference (RNAi) functional pathways. Loss of Dicer1 affects different developmental processes. Dicer1 is essential for retinal development and maintenance. DICER1 was recently shown to have another function of silencing the toxicity of Alu RNAs in retinal pigment epithelium (RPE) cells, which are involved in the pathogenesis of age related macular degeneration. In this study, we characterized a Dicer1 mutant fish line, which carries a nonsense mutation (W1457Ter) induced by N-ethyl-N-nitrosourea mutagenesis. Zebrafish DICER1 protein is highly conserved in the evolution. Zebrafish Dicer1 is expressed at the earliest stages of zebrafish development and persists into late developmental stages; it is widely expressed in adult tissues. Homozygous Dicer1 mutant fish (DICER1(W1457Ter/W1457Ter)) have an arrest in early growth with significantly smaller eyes and are dead at 14-18 dpf. Heterozygous Dicer1 mutant fish have similar retinal structure to that of control fish; the retinal pigment epithelium (RPE) cells are normal with no sign of degeneration at the age of 20 months.

Pathogenesis of X-linked RP3: insights from animal models.

Retinitis Pigmentosa (RP) is a genetically heterogeneous disorder characterized by rod and cone photoreceptor cell dysfunction. X-linked RP (XLRP) is one of the most severe forms of human retinal degeneration, as determined by age-of-set and progression, and accounts for six to 20 % of all RP cases. At least six XLRP loci have been identified, but RP3 is the major subtype of XLRP, accounting for 70 to 80 % of affected families. The RPGR gene is responsible for the RP3 form of XLRP and is mutated in 10-20 % of all RP patients. The pathogenesis of retinitis pigmentosa GTPase regulator (RPGR) mutant-causing RP is not clear, different animal models have been used to understand the pathogenesis of these diseases. In this brief review, we will summarize the functional characterization of RPGR and highlight recent studies in animal models, which will not only shed light on the disease mechanisms in XLRP but will also provide therapeutic strategies for RP treatment.

Zebrafish model for the genetic basis of X-linked retinitis pigmentosa.

Retinitis pigmentosa (RP) affects 1/4000 individuals in most populations, and X-linked RP (XLRP) is one of the most severe forms of human retinal degeneration. Mutations in both the retinitis pigmentosa GTPase regulator (RPGR) gene and retinitis pigmentosa 2 (RP2) gene account for almost all cases of XLRP. The functional roles of both RPGR and RP2 in the pathogenesis of XLRP are unclear. Due to the surprisingly high degree of functional conservation between human genes and their zebrafish orthologues, the zebrafish has become an important model for human retinal disorders. In this brief review, we summarize the functional characterization of XLRP-causing genes, RPGR and RP2, in zebrafish, and highlight recent studies that provide insight into the cellular functions of both genes. This will not only shed light on disease mechanisms in XLRP but will also provide a solid platform to test RP-causing mutants before proposing XLRP gene therapy trials.

Smith-method assessment of anterior chamber depth for screening for narrow anterior chamber angles.

PURPOSE: To compare the axial anterior chamber depth (ACD) using the Smith method, in patients under treatment for primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), with an age-matched control group. MATERIALS AND METHODS: Triplicate just-touching-slit-length (JTSL) measurements of the axial anterior chamber depth were determined in 198 eyes of 99 patients (39 control; 36 POAG; and 24 PACG) recruited from King Saud University clinics, Riyadh, Saudi Arabia. Goldmann tonometry and gonioscopy were carried out as a part of the patient's routine examination. Subjects with a history of intraocular surgery for glaucoma or any other anterior segment disease were excluded form the study. The average ACD estimate by the JTSL method were compared among the various groups. RESULTS: The average JTSL estimates were: Control group 2.33+/-0.68 mm (axial ACD estimate = JTSL estimate x 1.4); POAG group 1.98+/-0.97 mm; PACG group 0.65+/-0.41 mm. There was no significant reduction (P = 0.068) of the JTSL estimate in the POAG group, compared to the control group. There was a statistically significant (P < 0.001) reduction of the JTSL estimate in the PACG group, compared to both the control and POAG groups. CONCLUSION: The Smith-method JTSL technique may be used for non-invasive rapid screening, to help identify patients at risk of developing angle-closure, during routine examination of patients in the ophthalmology clinic.