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The development of therapies for retinal disorders is hampered by a lack of appropriate animal models. Higher nonhuman primates are the only animals with retinal structure similar to humans, including the presence of a macula and fovea. However, few nonhuman primate models of genetic retinal disease are known. We identified a lineage of rhesus macaques with a frameshift mutation in exon 3 of the BBS7 gene c.160delG (p.Ala54fs) that is predicted to produce a non-functional protein. In humans, mutations in this and other BBS genes cause Bardet-Biedl syndrome, a ciliopathy and a syndromic form of retinitis pigmentosa generally occurring in conjunction with kidney dysfunction, polydactyly, obesity, and/or hypogonadism. Three full- or half-sibling monkeys homozygous for the BBS7 c.160delG variant, at ages 3.5, 4 and 6 years old, displayed a combination of severe photoreceptor degeneration and progressive kidney disease. In vivo retinal imaging revealed features of severe macular degeneration, including absence of photoreceptor layers, degeneration of the retinal pigment epithelium, and retinal vasculature atrophy. Electroretinography in the 3.5-year-old case demonstrated loss of scotopic and photopic a-waves and markedly reduced and delayed b-waves. Histological assessments in the 4- and 6-year-old cases confirmed profound loss of photoreceptors and inner retinal neurons across the posterior retina, with dramatic thinning and disorganization of all cell layers, abundant microglia, absent or displaced RPE cells, and significant gliosis in the subretinal space. Retinal structure, including presence of photoreceptors, was preserved only in the far periphery. Ultrasound imaging of the kidneys revealed deranged architecture, and renal histopathology identified distorted contours with depressed, fibrotic foci and firmly adhered renal capsules; renal failure occurred in the 6-year-old case. Magnetic resonance imaging obtained in one case revealed abnormally low total brain volume and unilateral ventricular enlargement. The one male had abnormally small testes at 4 years of age, but polydactyly and obesity were not observed. Thus, monkeys homozygous for the BBS7 c.160delG variant closely mirrored several key features of the human BBS syndrome. This finding represents the first identification of a naturally-occurring nonhuman primate model of BBS, and more broadly the first such model of retinitis pigmentosa and a ciliopathy with an associated genetic mutation. This important new preclinical model will provide the basis for better understanding of disease progression and for the testing of new therapeutic options, including gene and cell-based therapies, not only for BBS but also for multiple forms of photoreceptor degeneration.

An adult female rhesus macaque presented during routine annual physical examination for evaluation of a 2.5‐cm diameter superficial ulcerated dermal lesion that was subsequently diagnosed as a systemic fungal infection caused by Cryptococcus gattii. Cryptococcus gattii is one of several basidiomycetic yeasts responsible for pulmonary, neurologic, and disseminated infections in humans and animals. This report describes the diagnosis, management, and clinical resolution of a C. gattii infection in an immunocompetent 5‐year‐old female rhesus macaque. [ABSTRACT FROM AUTHOR]

Approximately 20% of students experience reading failure each year. One of the difficulties associated with this large percentage is that it has been documented that pre-service teachers may not be receiving the most appropriate training regarding reading acquisition. The present study sought to determine if pre-service teachers were proficient in phonological processing skills and thus capable of learning concepts for which these skills are prerequisite. One-hundred sixty-four participants (85 pre-service teachers and 79 non-education majors) were administered the Comprehensive Test of Phonological Processing (CTOPP). The results indicated that pre-service teachers' phonological processing skills were sufficiently developed and not significantly different from non-education majors or from the CTOPP's normative sample. These students have the ability to learn the concepts related to the science of reading. Components of an appropriate curriculum for pre-service teachers such that they can acquire this knowledge are discussed.

Nonhuman primates (NHPs) are vital translational research models due to their high genetic, physiological, and anatomical homology with humans. The "golden" rhesus macaque (Macaca mulatta) phenotype is a naturally occurring, inherited trait with a visually distinct pigmentation pattern resulting in light blonde colored fur. Retinal imaging also reveals consistent hypopigmentation and occasional foveal hypoplasia. Here, we describe the use of genome-wide association in 2 distinct NHP populations to identify candidate variants in genes linked to the golden phenotype. Two missense variants were identified in the Tyrosinase-related protein 1 gene (Asp343Gly and Leu415Pro) that segregate with the phenotype. An additional and distinct association was also found with a Tyrosinase variant (His256Gln), indicating the light-colored fur phenotype can result from multiple genetic mechanisms. The implicated genes are related through their contribution to the melanogenesis pathway. Variants in these 2 genes are known to cause pigmentation phenotypes in other species and to be associated with oculocutaneous albinism in humans. The novel associations presented in this study will permit further investigations into the role these proteins and variants play in the melanogenesis pathway and model the effects of genetic hypopigmentation and altered melanogenesis in a naturally occurring nonhuman primate model. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate safety and efficacy of allotopic human ND4 for treatment of a Leber's hereditary optic neuropathy (LHON) mouse model harboring the G11778A mitochondrial mutation., Methods: We induced LHON in mice by intravitreal injection of mutant (G11778A) human ND4 DNA, responsible for most cases of LHON, that was directed to mitochondria using an AAV2 vector to which we appended a mitochondrial targeting sequence to the VP2 capsid. We then attempted rescue of visual loss using our test article (ScAAV2-P1ND4v2) containing a synthetic nuclear encoded G11778G ND4 gene that was allotopically expressed. Control mice either were uninjected or received AAV2-GFP or AAV2-mCherry. We performed RT-PCR and confocal microscopy at 2 weeks post injection. Pattern electroretinograms (PERGs), spectral-domain optical coherence tomography (SD-OCT), histology, and transmission electron microscopy (TEM) were performed. For toxicology and biodistribution studies, the test article was administered intravitreally to rats and rhesus macaques at different doses., Results: Mutant and wild-type ND4 were efficiently expressed in the mitochondria of retinal ganglion cells (RGCs). Visual function assessed by serial PERGs and retinal structure by serial SD-OCT showed a significant rescue by the test article. Histology and ultrastructural analysis confirmed that loss of RGCs and demise of axons was prevented by ScAAV2-P1ND4v2. Rat and nonhuman primate biodistribution studies showed that vector spread outside the injected eye into spleen and lymph nodes was minimal. Histopathology of tissues and organs including the eyes was comparable to that of uninfected and saline-injected eyes., Conclusions: Allotopically expressed wild-type ND4 prevents the phenotype induced by G11778A mitochondrial DNA with a toxicology profile acceptable for testing in a phase I clinical trial., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)