Sensitivity and specificity of the uniform field electroretinogram in glaucoma detection in comparison to the pattern electroretinogram.

Purpose: To determine the ability of the photopic negative response (PhNR) of the uniform field electroretinogram (UF-ERG) to identify early glaucomatous changes in comparison to the checkerboard and bar stimuli of the pattern electroretinogram (PERG).

Methods: Forty-nine glaucoma patients were classified into two groups: glaucoma-suspect (23 eyes) and early to moderate glaucoma (30 eyes), based on their clinical examination and the results of standard automated perimetry. Thirty patients (30 eyes) with intraocular pressures (IOP) of 21 mmHg or less, with no history of reported high IOP, were included as controls.

Safety and Efficacy of Adeno-Associated Viral Gene Therapy in Patients With Retinal Degeneration: A Systematic Review and Meta-Analysis.

Purpose: This systematic review evaluates the safety and efficacy of ocular gene therapy using adeno-associated virus (AAV).

Methods: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched systematically for controlled or non-controlled interventional gene therapy studies using key words related to retinal diseases, gene therapy, and AAV vectors.

Assessment of the uniform field electroretinogram for mouse retinal ganglion cell functional analysis.

Purpose: The uniform field electroretinogram (UF-ERG) has been suggested as an alternative to the pattern electroretinogram (PERG) for non-invasive assessment of retinal ganglion cell (RGC) function in primates. We evaluated the validity of the UF-ERG to assess mouse RGC activity in vivo.

Methods: Unilateral optic nerve crush (ONC) was performed on adult C57BL/6J mice.

Neonatal hyperoxia in mice triggers long-term cognitive deficits via impairments in cerebrovascular function and neurogenesis.

Preterm birth is the leading cause of death in children under 5 years of age. Premature infants who receive life-saving oxygen therapy often develop bronchopulmonary dysplasia (BPD), a chronic lung disease. Infants with BPD are at a high risk of abnormal neurodevelopment, including motor and cognitive difficulties.

XIAP gene therapy effects on retinal ganglion cell structure and function in a mouse model of glaucoma.

Glaucoma is a prevalent neurodegenerative disease that is characterized by progressive visual field loss. It is the leading cause of irreversible blindness in the world. The main risk factor for glaucoma is elevated intraocular pressure that results in the damage and death of retinal ganglion cells (RGCs) and their axons.

Sensory Experience Modulates Atrx-mediated Neuronal Integrity in the Mouse Retina.

Mutation of the α-thalassemia/mental retardation syndrome X-linked protein, ATRX, causes intellectual disability and is associated with pleiotropic defects including ophthalmological abnormalities. We have previously demonstrated that Atrx deficiency in the mouse retina leads to the selective loss of inhibitory interneurons and inner retinal dysfunction. Onset of the amacrine cell neurodegenerative phenotype in Atrx-deficient retinas occurs postnatally after neuronal specification, and coincides with eye opening.

XIAP Protects Retinal Ganglion Cells in the Mutant ND4 Mouse Model of Leber Hereditary Optic Neuropathy.

Purpose: Leber hereditary optic neuropathy (LHON) is a genetic form of vision loss that occurs primarily owing to mutations in the nicotinamide adenine dinucleotide dehydrogenase (ND) subunits that make up complex I of the electron transport chain. LHON mutations result in the apoptotic death of retinal ganglion cells. We tested the hypothesis that gene therapy with the X-linked inhibitor of apoptosis (XIAP) would prevent retinal ganglion cell apoptosis and reduce disease progression in a vector-induced mouse model of LHON that carries the ND4 mutation.

Overexpression of the X-Linked Inhibitor of Apoptosis Protects Against Retinal Degeneration in a Feline Model of Retinal Detachment.

Retinal detachment is an acute disorder in humans that is caused by trauma or disease, and it can often lead to permanent visual deficits that result from the death of photoreceptors in the retina. The final pathway for photoreceptor cell death is apoptosis and necroptosis. The X-linked inhibitor of apoptosis (XIAP) has been shown to block both of these cell death pathways.

Retinal interneuron survival requires non-cell-autonomous Atrx activity.

ATRX is a chromatin remodeling protein that is mutated in several intellectual disability disorders including alpha-thalassemia/mental retardation, X-linked (ATR-X) syndrome. We previously reported the prevalence of ophthalmological defects in ATR-X syndrome patients, and accordingly we find morphological and functional visual abnormalities in a mouse model harboring a mutation occurring in ATR-X patients. The visual system abnormalities observed in these mice parallels the Atrx-null retinal phenotype characterized by interneuron defects and selective loss of amacrine and horizontal cells.

Establishment of a cone photoreceptor transplantation platform based on a novel cone-GFP reporter mouse line.

We report successful retinal cone enrichment and transplantation using a novel cone-GFP reporter mouse line. Using the putative cone photoreceptor-enriched transcript Coiled-Coil Domain Containing 136 (Ccdc136) GFP-trapped allele, we monitored developmental reporter expression, facilitated the enrichment of cones, and evaluated transplanted GFP-labeled cones in wildtype and retinal degeneration mutant retinas. GFP reporter and endogenous Ccdc136 transcripts exhibit overlapping temporal and spatial expression patterns, both initiated in cone precursors of the embryonic retina and persisting to the adult stage in S and S/M opsin(+) cones as well as rod bipolar cells.

The Development of a Cat Model of Retinal Detachment and Re-attachment.

We present an optimized surgical technique for feline retinal detachment which allows for natural re-attachment, reduces retinal scarring and vitreal bands, and allows central placement of the detachment in close proximity to the optic nerve. This enables imaging via Optical Coherence Tomography (OCT) and multifocal electroretinography (mfERG) analysis. Ideal detachment conditions involve a lensectomy followed by a three-port pars plana vitrectomy.

A differential response to newt regeneration extract by C2C12 and primary mammalian muscle cells.

Background: Dedifferentiation, a process whereby differentiated cells lose their specialized characteristics and revert to a less differentiated state, plays a key role in the regeneration process in urodele amphibians such as the red spotted newt, Notophthalmus viridescens. Dedifferentiation of fully mature tissues is generally absent in mammalian cells. Previous studies have shown that mouse C2C12 multinucleated myotubes treated with extract derived from regenerating newt forelimbs can re-enter the cell cycle, fragment into mononucleated cells, and proliferate.

A focus on the optical properties of the regenerated newt lens.

Lens regeneration studies in the adult newt suggest that molecular aspects of lens regeneration are complete within 5 weeks of lentectomy. However, very little is known about the optical properties of the regenerated lens. In an aquatic environment, the lens accounts for almost all of the refractive power of the eye, and thus, a fully functional lens is critical.

Distinct roles for Ste20-like kinase SLK in muscle function and regeneration.

Background: Cell growth and terminal differentiation are controlled by complex signaling systems that regulate the tissue-specific expression of genes controlling cell fate and morphogenesis. We have previously reported that the Ste20-like kinase SLK is expressed in muscle tissue and is required for cell motility. However, the specific function of SLK in muscle tissue is still poorly understood.

Chitosan microparticles for delivery of proteins to the retina.

Chitosan microparticles (CMPs) have previously been developed for topical applications to the eye, but their safety and efficacy in delivering proteins to the retina have not been adequately evaluated. This study examines the release kinetics of CMPs in vitro, and assesses their biocompatibility and cytotoxicity on retinal cells in vitro and in vivo. Two proteins were used in the encapsulation and release studies: BSA (bovine serum albumin) and tat-EGFP (enhanced green fluorescent protein fused to the transactivator of transcription peptide).

Recovery of function following regeneration of the damaged retina in the adult newt, Notophthalmus viridescens.

The red-spotted newt, Notophthalmus viridescens, is one of few adult vertebrate organisms that has retained the remarkable ability to regenerate a complete retina following injury or removal. The aim of this study was to develop a non-invasive method to monitor recovery of components within the retinal circuitry, in vivo, following surgical removal (retinectomy) of the adult newt retina. A novel and reproducible protocol was established for full-field electroretinography in the intact newt retina.

XIAP therapy increases survival of transplanted rod precursors in a degenerating host retina.

Purpose: To assess the survival of rod precursor cells transplanted into the Rd9 mouse, a model of X-linked retinal degeneration, and the effect of antiapoptotic therapy with X-linked inhibitor of apoptosis (XIAP) on preventing cell loss.

Methods: Dissociated retinal cells from P4 Nrlp-GFP mice were transplanted into the subretinal space of 2-, 5-, and 8-month-old Rd9 mice. Histology, immunohistochemistry, and quantification of integrated cells were performed every month for up to 3 months after transplantation.

Smn deficiency causes neuritogenesis and neurogenesis defects in the retinal neurons of a mouse model of spinal muscular atrophy.

The eye is an excellent model for the study of neuronal development and pathogenesis of central nervous system disorders because of its relative ease of accessibility and the well-characterized cellular makeup. We have used this model to study spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disease caused by deletions or mutations in the survival of motor neuron 1 gene (SMN1). We have investigated the expression pattern of mouse Smn mRNA and protein in the neural retina and the optic nerve of wild type mice.

PEG-PLA microparticles for encapsulation and delivery of Tat-EGFP to retinal cells.

The efficient and controlled delivery of genes and proteins to retinal cells remains a challenge. In this study, we evaluated polyethylene glycol-polylactic acid (PEG-PLA) microparticles for encapsulation and delivery of a Transactivator of transcription-enhanced green fluorescent protein fusion (Tat-EGFP) to retinal cells. Our main objective was to develop a microparticle system that delivers Tat-EGFP with an initial rapid release (within 24 h) followed by a sustained release.

XIAP effects on retinal detachment-induced photoreceptor apoptosis [corrected].

Purpose: To evaluate the ability of X-linked inhibitor of apoptosis (XIAP) gene therapy to provide neuroprotection to cells of the outer nuclear layer (ONL) of the retina after retinal detachment.

Methods: Subretinal injections of a recombinant adenoassociated virus (rAAV) encoding either XIAP or green fluorescent protein (GFP; injection control) were performed in the left eye of Brown Norway rats. Two weeks later, retinal detachments were created at the site of viral injection by delivering sodium hyaluronate into the subretinal space.

XIAP protection of photoreceptors in animal models of retinitis pigmentosa.

Background: Retinitis pigmentosa (RP) is a blinding genetic disorder that is caused by the death of photoreceptors in the outer nuclear layer of the retina. To date, 39 different genetic loci have been associated with the disease, and 28 mutated genes have been identified. Despite the complexity of the underlying genetic basis for RP, the final common pathway is photoreceptor cell death via apoptosis.

Newt opportunities for understanding the dedifferentiation process.

Urodele amphibians, such as the newt Notophthalmus viridescens, have the unique ability to regenerate limbs, spinal cord, eye structures, and many vital organs through a process called epimorphic regeneration. Although the cellular basis of regeneration has been studied in detail, we know relatively little about the molecular controls of the process. This review provides an overview of forelimb regeneration in the newt, addressing what we know about cellular and molecular aspects.