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Synaptic Origins Of The Complex Receptive Field Structure In Primate Smooth Monostratified Retinal Ganglion Cells, Sara S Patterson, Rebecca J Girresch, Marcus A Mazzaferri, Andrea S Bordt, Wendy L Piñon-Teal, Brett D Jesse, Dinukie-Chantal W Perera, Melanie A Schlepphorst, James A Kuchenbecker, Alice Z Chuang, Jay Neitz, David W Marshak, Judith Mosinger Ogilvie

Journal Articles

Considerable progress has been made in studying the receptive fields of the most common primate retinal ganglion cell (RGC) types, such as parasol RGCs. Much less is known about the rarer primate RGC types and the circuitry that gives rise to noncanonical receptive field structures. The goal of this study was to analyze synaptic inputs to smooth monostratified RGCs to determine the origins of their complex spatial receptive fields, which contain isolated regions of high sensitivity called "hotspots." Interestingly, smooth monostratified RGCs co-stratify with the well-studied parasol RGCs and are thus constrained to receiving input from bipolar and amacrine cells …

Regulation Of Syntaxin3b-Mediated Membrane Fusion By T14, Munc18, And Complexin, Rajkishor Nishad, Miguel Betancourt-Solis, Himani Dey, Ruth Heidelberger, James A Mcnew

Journal Articles

Retinal neurons that form ribbon-style synapses operate over a wide dynamic range, continuously relaying visual information to their downstream targets. The remarkable signaling abilities of these neurons are supported by specialized presynaptic machinery, one component of which is syntaxin3B. Syntaxin3B is an essential t-SNARE protein of photoreceptors and bipolar cells that is required for neurotransmitter release. It has a light-regulated phosphorylation site in its N-terminal domain at T14 that has been proposed to modulate membrane fusion. However, a direct test of the latter has been lacking. Using a well-controlled in vitro fusion assay, we found that a phosphomimetic T14 syntaxin3B …

Synthetic Oct-A Blood Vessel Maps Using Fundus Images And Generative Adversarial Networks, Ivan Coronado, Samiksha Pachade, Emanuele Trucco, Rania Abdelkhaleq, Juntao Yan, Sergio Salazar-Marioni, Amanda Jagolino-Cole, Mozhdeh Bahrainian, Roomasa Channa, Sunil A Sheth, Luca Giancardo

Journal Articles

Vessel segmentation in fundus images permits understanding retinal diseases and computing image-based biomarkers. However, manual vessel segmentation is a time-consuming process. Optical coherence tomography angiography (OCT-A) allows direct, non-invasive estimation of retinal vessels. Unfortunately, compared to fundus images, OCT-A cameras are more expensive, less portable, and have a reduced field of view. We present an automated strategy relying on generative adversarial networks to create vascular maps from fundus images without training using manual vessel segmentation maps. Further post-processing used for standard en face OCT-A allows obtaining a vessel segmentation map. We compare our approach to state-of-the-art vessel segmentation algorithms trained …

Overcoming The Challenges To Clinical Development Of X-Linked Retinitis Pigmentosa Therapies: Proceedings Of An Expert Panel, David G Birch, Janet K Cheetham, Stephen P Daiger, Carel Hoyng, Christine Kay, Ian M Macdonald, Mark E Pennesi, Lori S Sullivan

Journal Articles

UNLABELLED: X-linked retinitis pigmentosa (XLRP) is a rare inherited retinal disease manifesting as impaired night vision and peripheral vision loss that progresses to legal blindness. Although several trials of ocular gene therapy for XLRP have been conducted or are in progress, there is currently no approved treatment. In July 2022, the Foundation Fighting Blindness convened an expert panel to examine relevant research and make recommendations for overcoming the challenges and capitalizing on the opportunities in conducting clinical trials of RPGR-targeted therapy for XLRP. Data presented concerned RPGR structure and mutation types known to cause XLRP, RPGR mutation-associated retinal phenotype diversity, …

Trogocytosis Of Neurons And Glial Cells By Microglia In A Healthy Adult Macaque Retina, Megan Goyal, Andrea S Bordt, Jay Neitz, David W Marshak

Journal Articles

Microglial cells are the primary resident immune cells in the retina. In healthy adults, they are ramified; that is, they have extensive processes that move continually. In adult retinas, microglia maintain the normal structure and function of neurons and other glial cells, but the mechanism underlying this process is not well-understood. In the mouse hippocampus, microglia engulf small pieces of axons and presynaptic terminals via a process called trogocytosis. Here we report that microglia in the adult macaque retina also engulf pieces of neurons and glial cells, but not at sites of synapses. We analyzed microglia in a volume of …

Synaptic Inputs To Displaced Intrinsically-Photosensitive Ganglion Cells In Macaque Retina, Andrea S Bordt, Sara S Patterson, James A Kuchenbecker, Marcus A Mazzaferri, Joel N Yearick, Emma R Yang, Judith Mosinger Ogilvie, Jay Neitz, David W Marshak

Journal Articles

Ganglion cells are the projection neurons of the retina. Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and also receive input from rods and cones via bipolar cells and amacrine cells. In primates, multiple types of ipRGCs have been identified. The ipRGCs with somas in the ganglion cell layer have been studied extensively, but less is known about those with somas in the inner nuclear layer, the "displaced" cells. To investigate their synaptic inputs, three sets of horizontal, ultrathin sections through central macaque retina were collected using serial block-face scanning electron microscopy. One displaced ipRGC received nearly all …

Review Of Evidence For Environmental Causes Of Uveal Coloboma, Evan B Selzer, Delphine Blain, Robert B Hufnagel, Philip J Lupo, Laura E Mitchell, Brian P Brooks

Journal Articles

Uveal coloboma is a condition defined by missing ocular tissues and is a significant cause of childhood blindness. It occurs from a failure of the optic fissure to close during embryonic development and may lead to missing parts of the iris, ciliary body, retina, choroid, and optic nerve. Because there is no treatment for coloboma, efforts have focused on prevention. While several genetic causes of coloboma have been identified, little definitive research exists regarding the environmental causes of this condition. We review the current literature on environmental factors associated with coloboma in an effort to guide future research and preventative …

Diagnostic Criteria For Detection Of Retinal Nerve Fibre Layer Thickness And Neuroretinal Rim Width Abnormalities In Glaucoma., Feihui Zheng, Marco Yu, Christopher Kai-Shun Leung

Journal Articles

BACKGROUND/AIMS: Although measurements of the Bruch's membrane opening minimum rim width (BMO-MRW) and retinal nerve fibre layer thickness (RNFLT) with optical coherence tomography (OCT) have been widely adopted in the diagnostic evaluation of glaucoma, there is no consensus on the diagnostic criteria to define BMO-MRW and RNFLT abnormalities. This study investigated the sensitivities and specificities of different diagnostic criteria based on the OCT classification reports for detection of glaucoma.

METHODS: 340 eyes of 137 patients with glaucoma and 87 healthy individuals, all with axial length ≤26mm, had global and sectoral BMO-MRW and RNFLT measured with Spectralis OCT (Heidelberg Engineering). Six …

Histamine Reduces Flash Sensitivity Of On Ganglion Cells In The Primate Retina, Nikolay P Akimov, David W Marshak, Laura J Frishman, Randolph D Glickman, Rafail G Yusupov

Journal Articles

PURPOSE. In Old World primates, the retina receives input from histaminergic neurons in the posterior hypothalamus. They are a subset of the neurons that project throughout the central nervous system and fire maximally during the day. The contribution of these neurons to vision, was examined by applying histamine to a dark-adapted, superfused baboon eye cup preparation while making extracellular recordings from peripheral retinal ganglion cells. METHODS. The stimuli were 5-ms, 560-nm, weak, full-field flashes in the low scotopic range. Ganglion cells with sustained and transient ON responses and two cell types with OFF responses were distinguished; their responses were recorded …

Syntaxin 3b Is Essential For The Exocytosis Of Synaptic Vesicles In Ribbon Synapses Of The Retina, L Curtis, P Datta, X Liu, N Bogdanova, R Heidelberger, R Janz

Journal Articles

Ribbon synapses of the vertebrate retina are specialized synapses that release neurotransmitter by synaptic vesicle exocytosis in a manner that is proportional to the level of depolarization of the cell. This release property is different from conventional neurons, in which the release of neurotransmitter occurs as a short-lived burst triggered by an action potential. Synaptic vesicle exocytosis is a calcium regulated process that is dependent on a set of interacting synaptic proteins that form the so-called SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) complex. Syntaxin 3B has been identified as a specialized SNARE molecule in ribbon synapses of the …

Elevated Albumin In Retinas Of Monkeys With Experimental Glaucoma, Louvenia Carter-Dawson, Yujin Zhang, Ronald S Harwerth, Ricky Rojas, Pramod Dash, Xinping C Zhao, Elizabeth Woldemussie, Guadalupe Ruiz, Alice Chuang, William P Dubinsky, John B Redell

Journal Articles

PURPOSE: To establish the identity of a prominent protein, approximately 70 kDa, that is markedly increased in the retina of monkeys with experimental glaucoma compared with the fellow control retina, the relationship to glaucoma severity, and its localization in the retina.

METHODS: Retinal extracts were subjected to 2-D gel electrophoresis to identify differentially expressed proteins. Purified peptides from the abundant 70 kDa protein were analyzed and identified by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) separation, and collision-induced dissociation sequencing. Protein identity was performed on MASCOT (Matrix Science, Boston, MA) and confirmed by Western blot. The relationship between the increase in this …

Syntaxin 3b Is A T-Snare Specific For Ribbon Synapses Of The Retina, Leigh B Curtis, Blair Doneske, Xiaoqin Liu, Christina Thaller, James A Mcnew, Roger Janz

Journal Articles

Previous studies have demonstrated that ribbon synapses in the retina do not contain the t-SNARE (target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor) syntaxin 1A that is found in conventional synapses of the nervous system. In contrast, ribbon synapses of the retina contain the related isoform syntaxin 3. In addition to its localization in ribbon synapses, syntaxin 3 is also found in nonneuronal cells, where it has been implicated in the trafficking of transport vesicles to the apical plasma membrane of polarized cells. The syntaxin 3 gene codes for four different splice forms, syntaxins 3A, 3B, 3C, and 3D. We demonstrate here …

Spatial Modulation Of Primate Inferotemporal Responses By Eye Position, Sidney R. Lehky, Xinmiao Peng, Carrie J. Mcadams, Anne B. Sereno

Journal Articles

BACKGROUND: A key aspect of representations for object recognition and scene analysis in the ventral visual stream is the spatial frame of reference, be it a viewer-centered, object-centered, or scene-based coordinate system. Coordinate transforms from retinocentric space to other reference frames involve combining neural visual responses with extraretinal postural information.

METHODOLOGY/PRINCIPAL FINDINGS: We examined whether such spatial information is available to anterior inferotemporal (AIT) neurons in the macaque monkey by measuring the effect of eye position on responses to a set of simple 2D shapes. We report, for the first time, a significant eye position effect in over 40% of …

Mechanisms Of Perceptual Learning Of Depth Discrimination In Random Dot Stereograms, Liat Gantz, Saumil S Patel, Susana T L Chung, Ronald S Harwerth

Journal Articles

Perceptual learning is a training induced improvement in performance. Mechanisms underlying the perceptual learning of depth discrimination in dynamic random dot stereograms were examined by assessing stereothresholds as a function of decorrelation. The inflection point of the decorrelation function was defined as the level of decorrelation corresponding to 1.4 times the threshold when decorrelation is 0%. In general, stereothresholds increased with increasing decorrelation. Following training, stereothresholds and standard errors of measurement decreased systematically for all tested decorrelation values. Post training decorrelation functions were reduced by a multiplicative constant (approximately 5), exhibiting changes in stereothresholds without changes in the inflection points. …

Stratification Of Alpha Ganglion Cells And On/Off Directionally Selective Ganglion Cells In The Rabbit Retina, Jian Zhang, Wei Li, Hideo Hoshi, Stephen L Mills, Stephen C Massey

Journal Articles

The correlation between cholinergic sensitivity and the level of stratification for ganglion cells was examined in the rabbit retina. As examples, we have used ON or OFF alpha ganglion cells and ON/OFF directionally selective (DS) ganglion cells. Nicotine, a cholinergic agonist, depolarized ON/OFF DS ganglion cells and greatly enhanced their firing rates but it had modest excitatory effects on ON or OFF alpha ganglion cells. As previously reported, we conclude that DS ganglion cells are the most sensitive to cholinergic drugs. Confocal imaging showed that ON/OFF DS ganglion cells ramify precisely at the level of the cholinergic amacrine cell dendrites, …

Genetic Networks Controlling Retinal Injury, Felix R Vazquez-Chona, Amna N Khan, Chun K Chan, Anthony N Moore, Pramod K Dash, M Rosario Hernandez, Lu Lu, Elissa J Chesler, Kenneth F Manly, Robert W Williams, Eldon E Geisert

Journal Articles

PURPOSE: The present study defines genomic loci underlying coordinate changes in gene expression following retinal injury.

METHODS: A group of acute phase genes expressed in diverse nervous system tissues was defined by combining microarray results from injury studies from rat retina, brain, and spinal cord. Genomic loci regulating the brain expression of acute phase genes were identified using a panel of BXD recombinant inbred (RI) mouse strains. Candidate upstream regulators within a locus were defined using single nucleotide polymorphism databases and promoter motif databases.

RESULTS: The acute phase response of rat retina, brain, and spinal cord was dominated by transcription …