Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The murine microphthalmia gene (Mitf) encodes a basic helix-loop-helix transcription factor thought to regulate transcription of genes encoding proteins of the pigmentation pathway. It may promote pigment cell survival and development. The protein encoded by Mitf appears to be critical for eye development, because mutant alleles demonstrate varying degrees of ocular malformation. One of the mildest of these is the Mitf vitiligo (Mitfvit) mutant allele, which exhibits uneven pigmentation of the retinal pigment epithelium (RPE) and slow, progressive photoreceptor cell loss, eventually leading to blindness. In the present study, the expression of Mitf during early eye development in the Mitfvit mutant was compared with that of pigmented wild type mice. Mitf expression quantified by reverse transcriptase-polymerase chain reaction amplification demonstrated a transient elevation of Mitf between embryonic day 10.5 (E10.5) and E13.5 in the Mitfvit mutant compared with wild type mice. In situ hybridization analysis confirmed this elevation and localized Mitf expression to the neuroepithelium during onset of optic vesicle formation (E9.0-E9.5) and, subsequently, to the RPE during optic cup formation (E10-E11.5) in both mutant and wild type eyes. This is the first report of transient elevation of Mitf in any of the Mitf mutants, and the elevation may be relevant to altered levels of pigmentation proteins as well as to the RPE abnormalities observed in the Mitfvit mutant.
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PMID:Transient overexpression of the Microphthalmia gene in the eyes of Microphthalmia vitiligo mutant mice. 982 64

Equine recurrent uveitis (ERU), a chronic, recurrent inflammation primarily of the anterior uveal tract, is the most common cause of blindness in horses. Recently, T-lymphocytes have been found to be the most numerous cell type to infiltrate the anterior uveal of horses with ERU. In the present study, we characterized the T-lymphocyte population in the anterior uveal tract of eyes of horses with chronic ERU by evaluating the microscopic appearance (histopathologic features), the T-lymphocyte subsets, and the relative levels and amounts of T-lymphocyte cytokine mRNA in the anterior uvea. Seven inflamed eyes (from six horses with chronic ERU) and 5 normal eyes (from five horses with nonocular problems) were studied. After clinical examination, the eyes were removed, ocular fluids were aspirated, and anterior uveal tissues (iris and ciliary body) were processed for histologic and molecular (RNA isolation) analyses. Histologic examination by hematoxylin and eosin (H and E) staining and immunohistochemistry evaluating T-lymphocyte subsets (anti-CD4, CD8, CD5) were performed for each sample. RNA samples were analyzed for levels of messenger (m) RNA specific for interleukin (IL)-2, 4, and interferon-gamma (IFNgamma) by quantitative reverse transcriptase polymerase chain reaction (QRT-PCR). Eyes with ERU exhibited characteristic clinical signs, including corneal edema, aqueous flare, posterior synechia, corpora nigra degeneration, and cataract formation. Histologically, infiltration of the uveal tract with lymphocytes, plasma cells, and macrophages was most evident in the ciliary body and base of the iris. Loss of tissue structure (destruction) was most evident in the ciliary processes. Infiltrating lymphocytes were predominantly CD4+ T-cells (e.g. 48% CD4+ and 18% CD8+ in the ciliary body stroma), as determined by immunohistochemistry. Few inflammatory cells were observed in the normal eyes. The QRT-PCR results revealed increased transcription of IL-2 and IFNgamma and low IL-4 mRNA expression in eyes with chronic ERU compared to normal eyes, demonstrating a Thelper (Th) 1-like inflammatory response in eyes with ERU.
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PMID:Characterization of T-lymphocytes in the anterior uvea of eyes with chronic equine recurrent uveitis. 1052 83

Diabetic retinopathy is the commonest complication of diabetes and is the biggest single cause of registered blindness in the UK. No biochemical tests exist to determine the precise state and rate of change of the eyes in the diabetic patient. In the present study, using real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR), we measured mRNA encoding the retina-specific pigment protein rhodopsin (RHO) in the peripheral blood of healthy individuals (n = 20) and diabetic patients (n = 46) with and without retinopathy. Beta-actin mRNA was also assayed and results are expressed as a ratio of RHO to beta-actin mRNA. Peripheral blood was taken by venipucture directly into PAXgene Blood RNA collection tubes and RNA extracted by use of the PAXgene Blood RNA extraction kit, as per the manufacturer's (Qiagen) instructions. Diabetic patients were divided into three groups defined by the severity of retinopathy as assessed by fundoscopy: A, diabetic without retinopathy; B, background retinopathy; and C, preproliferative retinopathy. Medians of the ratios between groups were compared. RHO mRNA was successfully detected and quantified in peripheral blood in all healthy and diabetic groups, with levels shown to be significantly higher in diabetic patients than in healthy controls (2.54 x 10(-5) vs. 1.29 x 10(-5); P = 0.002). Significant differences in RHO mRNA levels were also seen between healthy control subjects and diabetic groups A (2.52 x 10(-5); P = 0.022), B (1.98 x 10(-5); P = 0.028), and C (5.08 x 10(-5); P = 0.002). The results suggest that there is an increase in circulatory RHO mRNA with the severity of diabetic retinopathy.
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PMID:Real-time quantitative PCR measurement of circulatory rhodopsin mRNA in healthy subjects and patients with diabetic retinopathy. 1525 55

Neovascularization stimulated by IGF-1 mediated induction of vascular endothelial growth factor (VEGF) is one of the leading causes of blindness in humans. It plays a central role in the pathogenesis of proliferative diabetic retinopathy (DR), neovascular glaucoma, exudative age-related macular degeneration (AMD) and retinopathy of prematurity. Neovascularization is a multi-step process that involves complex interactions of a variety of mitogenic factors such as VEGF and IGF-I which are produced locally in the human eye by a variety of cells including retinal pigment epithelial (RPE) cells, retinal capillary pericytes, endothelial cells, Mueller cells and ganglion cells. We hypothesized that somatostatin would inhibit the IGF-1 signal transduction pathway in RPE cells, resulting in decreased VEGF production. We have observed expression of somatostatin receptor protein in retinal pigment epithelial (RPE) cells of the human eye using immunohistochemistry and have confirmed expression of somatostatin receptors in cultured human RPE cells using reverse transcriptase-PCR. IGF-1 induced a dose dependent increase in IGF-1R phosphorylation and in VEGF mRNA levels in cultured human RPE cells. Somatostatin and octreotide, a somatostatin analogue, inhibited IGF-1 receptor (IGF-1R) phosphorylation and decreased VEGF production. Both IGF-1R phosphorylation and accumulation of VEGF mRNA were inhibited by physiological levels of somatostatin and octreotide (1 nM). These results demonstrate somatostatin and octreotide mediated attenuation of both IGF-1R signal transduction and VEGF mRNA accumulation via somatostatin receptor type 2 (sst2). Furthermore, these data suggest a rationale for the use of octreotide as a prophylactic and therapeutic option in disease states that cause ocular neovascularization.
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PMID:Somatostatin inhibits IGF-1 mediated induction of VEGF in human retinal pigment epithelial cells. 1538 Oct 31

Glaucoma is a prevalent cause of blindness, resulting in the apoptotic death of retinal ganglion cells and optic nerve degeneration. The disease is often associated with elevated intraocular pressure, however, molecular mechanisms involved in ganglion cell death are poorly understood. To identify proteins contributing to this pathological process, we analysed the retinal gene expression of DBA/2J mice that develop an elevated intraocular pressure by the age of 6 months with subsequent ganglion cell loss. In this study, we identified subunits of the epithelial sodium channel (ENaC) family that are specifically expressed under elevated intraocular pressure. Using reverse transcriptase polymerase chain reaction we observed a significant increase of alpha-ENaC in the neuronal retina of DBA/2J mice when compared with control animals, while beta-ENaC and gamma-ENaC were not detectable in this tissue. Specific immune sera to ENaC subunits showed up-regulation of alpha-ENaC in synaptic and nuclear layers of the retina, and in the retinal pigment epithelium. Consistent with our polymerase chain reaction data, beta-ENaC was not detected by specific antibodies in the retina, while gamma-ENaC was only present in the retinal pigment epithelium under ocular hypertension. Finally, the increase of alpha-ENaC gene expression in the neuronal retina and the retinal pigment epithelium was not observed in other tissues of DBA/2J mice. Since the intraocular pressure is regulated by the transport of aqueous humour across epithelial structures of the eye that in turn is associated with ion flux, the specific up-regulation of ENaC proteins could serve as a protecting mechanism against elevated intraocular pressure.
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PMID:Subunits of the epithelial sodium channel family are differentially expressed in the retina of mice with ocular hypertension. 1595 55

The human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome (AIDS) pandemic has pervasive effects on culture, economics, policy, and human development. All organs can be affected by complications of HIV/AIDS, including the eye. When sufficient resources are available and widespread antiretroviral resistance does not exist, the four available classes of antiretroviral agents - nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and fusion inhibitors - can be combined to provide highly active antiretroviral therapy (HAART). For many (not all) patients, HAART converts an inexorably fatal disease into a chronic disease with a fairly good prognosis. Use of HAART often induces partial immune recovery, which has predominantly beneficial effects on ocular complications of AIDS. However, HAART-induced immune recovery sometimes results in immune recovery inflammatory syndromes, such as immune recovery uveitis. Use of HAART is the single most useful intervention for most patients with ocular complications of AIDS. However, specific ocular therapy is also critical to avoid blindness in the early months before immune recovery can occur, or if HAART is unavailable. Increasing availability of HAART worldwide shows great promise to alleviate one of the world's greatest plagues. However, predictable secular trends in the AIDS epidemic make it likely that the number of cases of ocular complications of AIDS will increase substantially before they decrease. Ophthalmologists worldwide should be familiar with the diagnosis and management of cytomegalovirus retinitis - the most common ocular complication of AIDS - and should establish partnerships with physicians who are able to provide HAART. Research is needed to determine the optimal approach for managing cytomegalovirus retinitis in resource-constrained settings.
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PMID:Medical management of human immunodeficiency virus infection. 1871 Dec 66

Infantile malignant osteopetrosis (arOP) is an autosomal recessive disorder. Mutations in the T-cell immune regulator 1 (TCIRG1) gene were found as the cause of arOP. We found the first Iranian patient with a rare gross deletion in this gene. The patient was a 5-year-old girl with macrocephaly, facial dysmorphism, blindness, mental retardation, hepatosplenomegaly, pancytopenia, and osteosclerotic changes in the skull and limb. Molecular analysis was performed using reverse transcriptase-polymerase chain reaction for exons 10-19 of the TCIRG1 gene followed by whole gene sequencing. She showed a 275 bp unexpected amplified segment. Sequencing revealed a gross deletion in exons 10-15 transcript region of TCIRG1 that affected codon 389 to 518. Various types of mutations in the TCIRG1 gene in arOP have been reported, however, gross deletions are reported rarely. This gross deletion is the first mutation reported among Iranian patients in this gene. This deletion is also the largest deletion of TCIRG1 gene reported to date.
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PMID:Rare gross deletion in T-cell immune regulator-1 gene in Iranian family with infantile malignant osteopetrosis. 1894 80

An outbreak of neurological disease occurred in pheasant chicks on a game farm in 2007. The disease was first seen in the 10th hatching of chicks on the farm. Affected chicks showed trembling and incoordination from the time of hatching, and subsequently blindness and cataract formation was seen in some of the affected chicks at 3 weeks of age. The peak mortality and culling figure was 21.0% in the worst affected hatch, compared with a maximum of 11.7% in the first nine hatches. No further cases were evident by 7.5 weeks of age. Histopathological examination showed a moderate acute encephalomyelitis in some, but not all, of the chicks with neurological signs. The clinical presentation and histopathological findings were typical of vertically transmitted avian encephalomyelitis as seen in chickens, although avian encephalomyelitis virus could not be detected in inoculated embryonated chicken eggs. However, serological testing by enzyme-linked immunosorbent assay for antibodies to the virus was positive in four of five affected 3-week-old birds and in 23 out of 29 adult breeding birds, and reverse transcriptase-polymerase chain reaction testing of RNA extracted from brain and pancreas tissue of affected chicks yielded nucleotide sequences aligned 82% and 83% with three avian encephalomyelitis sequences in a sequence database. The evidence suggested that the neurological disease was attributable to infection with a strain of avian encephalomyelitis virus that appeared to have entered the flock at the start of the breeding season, and was possibly introduced by carrier pheasants brought on to the farm early in the season.
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PMID:Avian encephalomyelitis virus in reared pheasants: a case study. 1946 44