@article {671, title = {Autism Linked to Increased Oncogene Mutations but Decreased Cancer Rate.}, journal = {PLoS One}, volume = {11}, year = {2016}, month = {2016}, pages = {e0149041}, abstract = {

Autism spectrum disorder (ASD) is one phenotypic aspect of many monogenic, hereditary cancer syndromes. Pleiotropic effects of cancer genes on the autism phenotype could lead to repurposing of oncology medications to treat this increasingly prevalent neurodevelopmental condition for which there is currently no treatment. To explore this hypothesis we sought to discover whether autistic patients more often have rare coding, single-nucleotide variants within tumor suppressor and oncogenes and whether autistic patients are more often diagnosed with neoplasms. Exome-sequencing data from the ARRA Autism Sequencing Collaboration was compared to that of a control cohort from the Exome Variant Server database revealing that rare, coding variants within oncogenes were enriched for in the ARRA ASD cohort (p<1.0 x 10(-8)). In contrast, variants were not significantly enriched in tumor suppressor genes. Phenotypically, children and adults with ASD exhibited a protective effect against cancer, with a frequency of 1.3\% vs. 3.9\% (p<0.001), but the protective effect decreased with age. The odds ratio of neoplasm for those with ASD relative to controls was 0.06 (95\% CI: 0.02, 0.19; p<0.0001) in the 0 to 14 age group; 0.35 (95\% CI: 0.14, 0.87; p = 0.024) in the 15 to 29 age group; 0.41 (95\% CI: 0.15, 1.17; p = 0.095) in the 30 to 54 age group; and 0.49 (95\% CI: 0.14, 1.74; p = 0.267) in those 55 and older. Both males and females demonstrated the protective effect. These findings suggest that defects in cellular proliferation, and potentially senescence, might influence both autism and neoplasm, and already approved drugs targeting oncogenic pathways might also have therapeutic value for treating autism.

}, keywords = {Adolescent, Adult, Autism Spectrum Disorder, Child, Child, Preschool, Female, Genes, Tumor Suppressor, Genetic Predisposition to Disease, Humans, Infant, Male, Middle Aged, Mutation, Neoplasms, Oncogenes, Prevalence, Young Adult}, issn = {1932-6203}, doi = {10.1371/journal.pone.0149041}, author = {Darbro, Benjamin W and Singh, Rohini and Zimmerman, M Bridget and Mahajan, Vinit B and Bassuk, Alexander G} } @article {645, title = {COMBINED VITRECTOMY AND INTRAVITREAL DEXAMETHASONE (OZURDEX) SUSTAINED-RELEASE IMPLANT.}, journal = {Retina}, volume = {36}, year = {2016}, month = {2016 Nov}, pages = {2087-2092}, abstract = {

PURPOSE: To evaluate the safety and efficacy of combining intravitreal dexamethasone implantation (Ozurdex) with pars plana vitrectomy (PPV).

METHODS: A retrospective review was conducted on cases where Ozurdex injection was performed in the operating room in conjunction with pars plana vitrectomy. Our primary outcome measure was the presence of surgical complications in the perioperative and 3-month postoperative window. We also measured visual acuity, intraocular pressure (IOP), and macular edema at baseline, one, and 3 months after surgery.

RESULTS: Fifteen eyes in 14 cases were reviewed. There were no complications intraoperatively or at 1-month postoperatively. Two patients (2 eyes) with prior retinal detachment developed proliferative vitreoretinopathy and redetachment at 3 months. Visual acuity improved in 7 of 15 eyes, and an average improvement of 2 lines was achieved for the entire cohort. There was no overall change in intraocular pressure although 1 patient developed an increase in intraocular pressure \>5 mmHg. Five of 9 patients with baseline macular edema experienced improvement or resolution at 3 months.

CONCLUSION: Intraoperative Ozurdex in combination with PPV may be safe and effective in treating macular edema caused by many different underlying diseases.

}, keywords = {Adult, Aged, Aged, 80 and over, Combined Modality Therapy, Dexamethasone, Drug Implants, Female, Glucocorticoids, Humans, Intraocular Pressure, Intravitreal Injections, Macular Edema, Male, Middle Aged, Retinal Vein Occlusion, Retrospective Studies, Tomography, Optical Coherence, Uveitis, Posterior, Visual Acuity, Vitrectomy, Wet Macular Degeneration}, issn = {1539-2864}, doi = {10.1097/IAE.0000000000001063}, author = {Zheng, Andrew and Chin, Eric K and Almeida, David R P and Tsang, Stephen H and Mahajan, Vinit B} } @article {677, title = {Precision Medicine: Personalized Proteomics for the Diagnosis and Treatment of Idiopathic Inflammatory Disease.}, journal = {JAMA Ophthalmol}, volume = {134}, year = {2016}, month = {2016 Apr}, pages = {444-8}, abstract = {

IMPORTANCE: To better characterize posterior uveitis, vitreous samples from 15 patients were subjected to antibody arrays, and the expression levels of 200 human cytokines were evaluated. Expression was analyzed by 1-way analysis of variance (significance at P < .01), unsupervised cluster algorithm, and pathway analysis.

OBSERVATIONS: Unbiased clustering of patients, based on their cytokine expression profile, suggested that particular protein networks and molecular pathways are altered in various forms of uveitis. Expression of interleukin 23 (IL-23), IL-1 receptor I (IL-1RI), IL-17R, tissue inhibitors of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2), insulinlike growth factor-binding protein 2 (IGFBP-2), nerve growth factor (b-NGF), platelet-derived growth factor receptor β polypeptide (PDGFRb), bone morphogenic protein 4 (BMP-4), and stem cell factor (SCF) constituted a common cytokine signature in the vitreous of patients with uveitis. In 1 patient with progressive, idiopathic visual loss, this last-line analysis implicated retinal autoimmunity, a diagnosis that was validated when her serum sample was found to contain antibodies to S-arrestin, a retinal protein and potent cause of autoimmune retinal degeneration.

CONCLUSIONS AND RELEVANCE: The analysis identifies a common cytokine signature for posterior uveitis and guides the diagnosis of a patient with idiopathic uveitis. Personalized treatment reversed the visual loss, illustrating how proteomic tools may individualize therapy.

}, keywords = {Adrenal Cortex Hormones, Adult, Analysis of Variance, Case-Control Studies, Cytokines, Follow-Up Studies, Humans, Immunosuppressive Agents, Male, Middle Aged, Precision Medicine, Proteomics, Reference Values, Risk Assessment, Severity of Illness Index, Treatment Outcome, Uveitis, Visual Acuity}, issn = {2168-6173}, doi = {10.1001/jamaophthalmol.2015.5934}, author = {Velez, Gabriel and Roybal, C Nathaniel and Colgan, Diana and Tsang, Stephen H and Bassuk, Alexander G and Mahajan, Vinit B} } @article {687, title = {Intravitreal Anti-VEGF Injections in Pregnancy: Case Series and Review of Literature.}, journal = {J Ocul Pharmacol Ther}, volume = {31}, year = {2015}, month = {2015 Dec}, pages = {605-10}, abstract = {

The use of intravitreal antivascular endothelial growth factor (anti-VEGF) injection is gaining wide acceptance as an off-label therapy for diseases that may affect pregnant women. However, these drugs may cause systemic side effects in the mother and fetal harm. This could lead specialists to not administer the drug or women to abort the fetus or to refuse treatment during pregnancy. We report the course of pregnancy in 3 women treated with intravitreal bevacizumab and provide a review of the literature on the use of intravitreal anti-VEGF in pregnancy. Our patients did not have any drug-related adverse event and delivered healthy full-term infants, although one of the women had risk factors for miscarriage. Infants reached all developmental milestones appropriately during infancy. A literature search on the use of intravitreal anti-VEGF injection in pregnancy was undertaken. Data for this review were identified by searches of PubMed and references from relevant articles using the search terms "pegaptanib," "bevacizumab," "ranibizumab," "aflibercept," "anti-VEGF," "intravitreal injection," "pregnant," "pregnancy," "abortion," "miscarriage," "preeclampsia," "embryo-fetal toxicity," "fetal malformations," "teratogenesis," "adverse events," and "maternofetal complications" in multiple combinations. We believe that intravitreal anti-VEGF can be given during pregnancy only when potential benefit to the woman justifies the potential risks to the fetus. When making a decision about whether to give drugs during pregnancy, it is important to consider the timing of exposure and its relationship to windows of developmental sensitivity. We believe that this review will be useful to specialists to inform and possibly treat their pregnant patients.

}, keywords = {Adult, Angiogenesis Inhibitors, Bevacizumab, Female, Humans, Infant, Newborn, Intravitreal Injections, Pregnancy, Pregnancy Complications, Pregnancy Outcome, Risk Factors, Vascular Endothelial Growth Factor A}, issn = {1557-7732}, doi = {10.1089/jop.2015.0056}, author = {Polizzi, Silvio and Mahajan, Vinit B} } @article {701, title = {Macular Hole Closure With Internal Limiting Membrane Abrasion Technique.}, journal = {JAMA Ophthalmol}, volume = {133}, year = {2015}, month = {2015 Jun}, pages = {635-41}, abstract = {

IMPORTANCE: Internal limiting membrane (ILM) abrasion is an alternative surgical technique for successful full-thickness macular hole (MH) repair.

OBJECTIVE: To study the effects of ILM abrasion as an alternative method of MH repair.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective consecutive case series from January 2006 to December 2008. Demographic data and preoperative, intraoperative, and postoperative examination records of all patients were reviewed for patients who underwent ILM abrasion with a diamond-dusted membrane scraper during vitrectomy for MH repair. A total of 100 eyes underwent ILM abrasion as an alternative to traditional ILM peeling.

MAIN OUTCOMES AND MEASURES: Rate of MH closure and visual acuity (VA) outcomes at 3 months after surgery.

RESULTS: Macular hole closure was achieved with a single surgical procedure in 94 of 100 eyes (94.0\%; 95\% CI, 87.4\%-97.8\%). Among all patients, the median preoperative VA was 20/100 (range, 20/30 to hand motions; 25th quartile, 20/60; and 75th quartile, 20/160), and the median postoperative VA at 3 months after surgery was 20/60 (range, 20/20 to hand motions; 25th quartile, 20/40; and 75th quartile, 20/100). Among all patients with stage 2 MHs, 30 of 38 patients (78.9\%) had at least 2 lines of VA gain: 15 of 23 (65.2\%) were phakic, and 15 of 15 (100\%) were pseudophakic. Four of 38 patients (10.5\%) with stage 2 MHs had at least 2 lines of VA loss, and all were phakic. Among all patients with stage 3 or 4 MHs, 42 of 62 (67.7\%) had at least 2 lines of VA gain, of which 30 of 38 (78.9\%) were phakic and 22 of 24 (91.7\%) were pseudophakic. Six of 62 patients (9.7\%) with stage 3 or 4 MHs had at least 2 lines of VA loss: 4 were phakic, and 2 were pseudophakic. In total, 35.0\% (95\% CI, 25.7\%-44.3\%) of patients achieved 20/40 vision or better, and 52.0\% (95\% CI, 42.2\%-61.8\%) of patients achieved 20/50 vision or better.

CONCLUSIONS AND RELEVANCE: Abrasion of the ILM with a diamond-dusted membrane scraper at the time of vitrectomy achieves high rates of MH closure. This technique avoids complete removal of the retinal ILM basement membrane and subjacent tissues and appears to provide MH closure rates similar to those of traditional ILM peeling.

}, keywords = {Adult, Aged, Aged, 80 and over, Basement Membrane, Endotamponade, Female, Fluorocarbons, Humans, Male, Middle Aged, Ophthalmologic Surgical Procedures, Prone Position, Retinal Perforations, Retrospective Studies, Sulfur Hexafluoride, Tomography, Optical Coherence, Visual Acuity, Vitrectomy}, issn = {2168-6173}, doi = {10.1001/jamaophthalmol.2015.204}, author = {Mahajan, Vinit B and Chin, Eric K and Tarantola, Ryan M and Almeida, David R P and Somani, Riz and Boldt, H Culver and Folk, James C and Gehrs, Karen M and Russell, Stephen R} } @article {685, title = {Management of Choroidal Granulomas Involving the Macula in Corticosteroid-Intolerant Patients.}, journal = {JAMA Ophthalmol}, volume = {133}, year = {2015}, month = {2015 Nov}, pages = {1351-2}, keywords = {Adult, Choroid Diseases, Combined Modality Therapy, Dexamethasone, Drug Therapy, Combination, Drug Tolerance, Folic Acid Antagonists, Glucocorticoids, Granuloma, Humans, Interferon-gamma Release Tests, Intravitreal Injections, Macula Lutea, Male, Methotrexate, Tuberculoma, Tuberculosis, Ocular, Vitrectomy}, issn = {2168-6173}, doi = {10.1001/jamaophthalmol.2015.1951}, author = {Chin, Eric K and Almeida, David R P and Mahajan, Vinit B} } @article {713, title = {Quantitative autofluorescence as a clinical tool for expedited differential diagnosis of retinal degeneration.}, journal = {JAMA Ophthalmol}, volume = {133}, year = {2015}, month = {2015 Feb}, pages = {219-20}, keywords = {Adult, ATP-Binding Cassette Transporters, Diagnosis, Differential, DNA, DNA Mutational Analysis, Fluorescein Angiography, Fundus Oculi, Humans, Male, Mutation, Optical Imaging, Retina, Retinal Degeneration, Retinitis Pigmentosa}, issn = {2168-6173}, doi = {10.1001/jamaophthalmol.2014.4507}, author = {Marsiglia, Marcela and Lee, Winston and Mahajan, Vinit B and Zernant, Jana and Delori, Fran{\c c}ois C and Tsang, Stephen H and Sparrow, Janet R} } @article {725, title = {Decreased macular thickness in nonproliferative macular telangiectasia type 2 with oral carbonic anhydrase inhibitors.}, journal = {Retina}, volume = {34}, year = {2014}, month = {2014 Jul}, pages = {1400-6}, abstract = {

PURPOSE: To evaluate whether carbonic anhydrase inhibitors reduce the macular thickness and/or cystic spaces in patients with macular telangiectasia (MacTel) Type 2.

METHODS: Retrospective review of patients with nonproliferative cystoid changes associated with MacTel seen at the University of Iowa between 2009 and 2012. Carbonic anhydrase inhibitors were used in 8 patients with MacTel Type 2. Five patients with MacTel Type 2 were observed during this period. Initial and final visual acuities were documented. The presence of cystic spaces and the retinal thickness were measured with spectral-domain optical coherence tomography.

RESULTS: Patients treated with oral carbonic anhydrase inhibitors showed significant reduction in both the cystoid cavities and central macular thickness when compared with the patients who were observed (-12.2 μm; P = 0.020). The reduction in retinal thickness was more pronounced in patients receiving acetazolamide (-20.13 μm; P = 0.007) compared with methazolamide (-6.25 μm; P = 0.177). There was no significant change in visual acuity in patients receiving carbonic anhydrase inhibitors. Five patients with MacTel Type 2 did not receive treatment and demonstrated no change in visual acuity, cystoid cavities, or central macular thickness.

CONCLUSION: Oral carbonic anhydrase inhibitors, particularly acetazolamide, may decrease macular cystic cavities and reduce central macular thickness but does not appear to improve visual acuity. These findings have yet to be confirmed with a prospective treatment trial.

}, keywords = {Acetazolamide, Administration, Oral, Adult, Aged, Carbonic Anhydrase Inhibitors, Female, Fluorescein Angiography, Humans, Male, Methazolamide, Middle Aged, Organ Size, Retina, Retinal Telangiectasis, Retrospective Studies, Tomography, Optical Coherence, Visual Acuity}, issn = {1539-2864}, doi = {10.1097/IAE.0000000000000093}, author = {Chen, John J and Sohn, Elliott H and Folk, James C and Mahajan, Vinit B and Kay, Christine N and Boldt, H Culver and Russell, Stephen R} } @article {765, title = {Intravitreal bevacizumab for peripapillary choroidal neovascular membranes.}, journal = {Arch Ophthalmol}, volume = {130}, year = {2012}, month = {2012 Aug}, pages = {1073-5}, keywords = {Adult, Aged, Aged, 80 and over, Angiogenesis Inhibitors, Antibodies, Monoclonal, Humanized, Bevacizumab, Choroidal Neovascularization, Female, Fluorescein Angiography, Humans, Intravitreal Injections, Macular Degeneration, Male, Middle Aged, Retreatment, Subretinal Fluid, Tomography, Optical Coherence, Treatment Outcome, Vascular Endothelial Growth Factor A, Visual Acuity}, issn = {1538-3601}, doi = {10.1001/archophthalmol.2012.465}, author = {Davis, Andrew S and Folk, James C and Russell, Stephen R and Sohn, Elliott H and Sohn, Elliot H and Boldt, H Culver and Stone, Edwin M and Mahajan, Vinit B} } @article {151, title = {Seroreactivity against aqueous-soluble and detergent-soluble retinal proteins in posterior uveitis.}, journal = {Archives of ophthalmology}, volume = {129}, year = {2011}, month = {2011 Apr}, pages = {415-20}, abstract = {

To characterize the seroreactivity against retinal proteins in patients with posterior uveitis, retinal disease of noninflammatory origin, and healthy controls.

}, keywords = {Adolescent, Adult, Autoantibodies, Autoantigens, Blotting, Western, Electrophoresis, Polyacrylamide Gel, Eye Proteins, Female, Humans, Immunoglobulin A, Immunoglobulin G, Immunoglobulin M, Male, Middle Aged, Retina, Retinal Degeneration, Solubility, Uveitis, Posterior, Young Adult}, author = {Ko, Audrey C and Brinton, Jason P and Mahajan, Vinit B and Zimmerman, Bridget and Brinton, Gregory S and Stone, Edwin M and Folk, James C and Mullins, Robert F} } @article {783, title = {Uveitis following intravitreal bevacizumab: a non-infectious cluster.}, journal = {Ophthalmic Surg Lasers Imaging}, volume = {42}, year = {2011}, month = {2011 Jul-Aug}, pages = {292-6}, abstract = {

BACKGROUND AND OBJECTIVE: In this retrospective case series, the authors report seven cases of bevacizumab-related uveitis that occurred within a 4-month period.

PATIENTS AND METHODS: Seven eyes of six patients developed non-infectious uveitis following bevacizumab intravitreal injections in a cohort of 978 consecutive bevacizumab injections.

RESULTS: The mean age of patients was 74.6 years (range: 26 to 92). All patients developed symptom onset within 1 day of injection. Shared signs and symptoms included corneal edema, anterior chamber and vitreous cell, conjunctival injection, ocular pain, and lack of hypopyon. In all patients, visual acuity returned to within one line of baseline acuity. All seven eyes had been previously injected with bevacizumab, with a mean number of antecedent injections of 6.1 (range: 3 to 12).

CONCLUSION: A cluster of sterile bevacizumab-related uveitic reactions was described in this case series. Acute onset of symptoms, absence of hypopyon, a predominant anterior segment reaction, and prompt improvement on topical steroid therapy are useful clinical features distinguishing this uveitic syndrome from infectious endophthalmitis.

}, keywords = {Adult, Aged, Aged, 80 and over, Angiogenesis Inhibitors, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Bevacizumab, Humans, Immunosuppressive Agents, Intravitreal Injections, Middle Aged, Retrospective Studies, Uveitis, Anterior, Vascular Endothelial Growth Factor A, Visual Acuity}, issn = {1938-2375}, doi = {10.3928/15428877-20110603-04}, author = {Kay, Christine N and Tarantola, Ryan M and Gehrs, Karen M and Folk, James C and Mahajan, Vinit B and Boldt, H Culver and Syed, Nasreen A and Russell, Stephen R} } @article {161, title = {Intravitreal bevacizumab during pregnancy.}, journal = {Retina (Philadelphia, Pa.)}, volume = {30}, year = {2010}, month = {2010 Oct}, pages = {1405-11}, abstract = {

To report the clinical course of four women treated with intravitreal bevacizumab during pregnancy.

}, keywords = {Adult, Angiogenesis Inhibitors, Antibodies, Monoclonal, Choroidal Neovascularization, Eye Infections, Fungal, Female, Follow-Up Studies, Gestational Age, Histoplasmosis, Humans, Intravitreal Injections, Off-Label Use, Pregnancy, Pregnancy Complications, Sarcoidosis, Tomography, Optical Coherence, Uveitis, Vascular Endothelial Growth Factor A, Visual Acuity}, author = {Tarantola, Ryan M and Folk, James C and Boldt, H Culver and Mahajan, Vinit B} } @article {163, title = {Patients with an acute zonal occult outer retinopathy-like illness rapidly improve with valacyclovir treatment.}, journal = {American journal of ophthalmology}, volume = {150}, year = {2010}, month = {2010 Oct}, pages = {511-8}, abstract = {

To describe 3 cases of an acute zonal occult outer retinopathy-like illness responsive to valacyclovir hydrochloride.

}, keywords = {Acute Disease, Acyclovir, Adolescent, Adult, Antiviral Agents, Electroretinography, Eye Infections, Viral, Female, Herpesviridae Infections, Humans, Male, Retinal Diseases, Retrospective Studies, Scotoma, Tomography, Optical Coherence, Valine, Visual Field Tests, Visual Fields}, author = {Mahajan, Vinit B and Stone, Edwin M} } @article {169, title = {A head-tilt test for hypopyon after intravitreal triamcinolone.}, journal = {Retina (Philadelphia, Pa.)}, volume = {29}, year = {2009}, month = {2009 Apr}, pages = {560-1}, keywords = {Adult, Anterior Chamber, Diagnosis, Differential, Diagnostic Techniques, Ophthalmological, Endophthalmitis, Eye Infections, Female, Glucocorticoids, Head, Humans, Inflammation, Injections, Posture, Triamcinolone Acetonide, Vitreous Body}, author = {Mahajan, Vinit B and Folk, James C and Boldt, H Culver} } @article {171, title = {Management of sympathetic ophthalmia with the fluocinolone acetonide implant.}, journal = {Ophthalmology}, volume = {116}, year = {2009}, month = {2009 Mar}, pages = {552-557.e1}, abstract = {

We examined whether implantation of the fluocinolone acetonide (Retisert) implant achieved control of inflammation and a reduced need for oral corticosteroids or immunosuppressives in patients with sympathetic ophthalmia (SO).

}, keywords = {Adult, Aged, Drug Implants, Female, Fluocinolone Acetonide, Follow-Up Studies, Glucocorticoids, Humans, Immunosuppressive Agents, Intraocular Pressure, Male, Middle Aged, Ophthalmia, Sympathetic, Retrospective Studies, Treatment Outcome, Visual Acuity}, author = {Mahajan, Vinit B and Gehrs, Karen M and Goldstein, Debra A and Fischer, David H and Lopez, Juan S and Folk, James C} } @article {173, title = {A new macular dystrophy with anomalous vascular development, pigment spots, cystic spaces, and neovascularization.}, journal = {Archives of ophthalmology}, volume = {127}, year = {2009}, month = {2009 Nov}, pages = {1449-57}, abstract = {

To clinically phenotype an inherited macular dystrophy with peculiar intraretinal pigment spots, cysts, and hemorrhage in a 24-year-old female proband and her family.

}, keywords = {Adolescent, Adult, Amblyopia, Child, Child, Preschool, Cysts, Electroretinography, Female, Fluorescein Angiography, Humans, Macular Degeneration, Male, Middle Aged, Pedigree, Phenotype, Retinal Hemorrhage, Retinal Neovascularization, Retinal Pigment Epithelium, Retinal Vessels, Strabismus, Tomography, Optical Coherence, Visual Acuity, Young Adult}, author = {Mahajan, Vinit B and Russell, Stephen R and Stone, Edwin M} } @article {177, title = {Transgenic mice carrying the H258N mutation in the gene encoding the beta-subunit of phosphodiesterase-6 (PDE6B) provide a model for human congenital stationary night blindness.}, journal = {Human mutation}, volume = {28}, year = {2007}, month = {2007 Mar}, pages = {243-54}, abstract = {

Mutations in the beta-subunit of cGMP-phosphodiesterase (PDE6beta) can lead to either progressive retinal disease, such as human retinitis pigmentosa (RP), or stationary disease, such as congenital stationary night blindness (CSNB). Individuals with CSNB in the Rambusch pedigree were found to carry the H258N allele of PDE6B (MIM$\#$ 180072); a similar mutation was not found in RP patients. This report describes an individual carrying the H258N allele, who presented with generalized retinal dysfunction affecting the rod system and a locus of dysfunction at the rod-bipolar interface. Also described are preclinical studies in which transgenic mice with the H258N allele were generated to study the pathophysiological mechanisms of CSNB. While Pde6b(rd1)/Pde6b(rd1) mice have severe photoreceptor degeneration, as in human RP, the H258N transgene rescued these cells. The cGMP-PDE6 activity of dark-adapted H258N mice showed an approximate three-fold increase in the rate of retinal cGMP hydrolysis: from 130.1 nmol x min(-1) x nmol(-1) rhodopsin in wild-type controls to 319.2 nmol x min(-1) x nmol(-1) rhodopsin in mutants, consistent with the hypothesis that inhibition of the PDE6beta activity by the regulatory PDE6gamma subunit is blocked by this mutation. In the albino (B6CBA x FVB) F2 hybrid background, electroretinograms (ERG) from H258N mice were similar to those obtained from affected Rambusch family members, as well as humans with the most common form of CSNB (X-linked), demonstrating a selective loss of the b-wave with relatively normal a-waves. When the H258N allele was introduced into the DBA background, there was no evidence of selective reduction in b-wave amplitudes; rather a- and b-wave amplitudes were both reduced. Thus, factors other than the PDE6B mutation itself could contribute to the variance of an electrophysiological response. Therefore, caution is advisable when interpreting physiological phenotypes associated with the same allele on different genetic backgrounds. Nevertheless, such animals should be of considerable value in further studies of the molecular pathology of CSNB.

}, keywords = {Adult, Animals, Cyclic Nucleotide Phosphodiesterases, Type 6, Disease Models, Animal, DNA Mutational Analysis, Electroretinography, Female, Humans, Male, Mice, Mice, Inbred DBA, Mice, Transgenic, Mutation, Night Blindness, Phosphoric Diester Hydrolases, Retinal Degeneration, Transgenes}, author = {Tsang, Stephen H and Woodruff, Michael L and Jun, Lin and Mahajan, Vinit and Yamashita, Clyde K and Pedersen, Robert and Lin, Chyuan-Sheng and Goff, Stephen P and Rosenberg, Thomas and Larsen, Michael and Farber, Debora B and Nusinowitz, Steven} }