Steven Fliesler | SUNY: University at Buffalo (original) (raw)

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Papers by Steven Fliesler

Research paper thumbnail of The subretinal drusenoid deposit (SDD) of age-related macular degeneration (AMD) may have a specific and strong association with high-risk vascular diseases (HRVDs)

Research paper thumbnail of Chemistry and metabolism of lipids in the vertebrate retina

Progress in Lipid Research, 1983

I. INTRODUCTION II. CELLULAR ORGANIZATION OF THE VERTEBRATE RETINA II1. STRUCTURAL ORGANIZATION O... more I. INTRODUCTION II. CELLULAR ORGANIZATION OF THE VERTEBRATE RETINA II1. STRUCTURAL ORGANIZATION OF VERTEBRATE PHOTORECEPTOR CELLS IV. LIPID COMPOSITION OF THE VERTEBRATE RETINA A. Historical considerations and general composition B. Phospholipid class composition C. Fatty acid composition D. Neutral lipids E. Glycolipids and other polar lipids V. LIPID COMPOSITION OF VERTEBRATE PHOTORECEPTOR OUTER SEGMENT MEMBRANES A. Preparation B. General composition C. Lipid class composition I. Phospholipids 2. Neutral lipids D. Fatty acid composition and phospholipid molecular species E. Molecular organization of lipids in rod outer segment disc membranes VI. LIPID METABOLISM IN THE VERTEBRATE RETINA A. Glyceride biosynthesis B. Fatty acids biosynthesis C. Ganglioside biosynthesis D. Sterol biosynthesis E. Phospholipid transfer proteins F. Base exchange reactions VII. LIPID METABOLISM 1N THE VERTEBRATE PHOTORECEPTOR CELLS A. Renewal and turnover of photoreceptor outer segment membranes 1. Renewal mechanisms 2. Proteins 3. Lipids B. Decarboxylation of phosphatidylserine to phosphatidylethanolamine C. Transmethylation of phosphatidylethanolamine to phosphatidylcholine VIII. EFFECT OF LIGHT ON THE METABOLISM OF RETINAL LIPIDS A. Gangliosides B. Phospholipids (other than inositides) C. Inositol phosphatides IX. THE IMPORTANCE OF LIP1DS IN NORMAL RETINA FUNCTION A. Lateral and rotational mobility of rhodopsin B. Rhodopsin orientation C. Rhodopsin regeneration and spectroscopic properties D. Thermal stability of rhodopsin E. Photobleaching of rhodopsin F. Effects of dietary manipulations on lipids of the retina X. ROLE OF LIPID PEROXIDATION IN RETINAL DEGENERATION A. Morphological changes in retinas exposed to pro-oxidant conditions B. Evidence for lipid peroxide accumulation in retinal degeneration C. Functional changes related to retinal lipid peroxides XI. CONCLUSIONS AND PERSPECTIVES

Research paper thumbnail of Onecut 1 Is Essential For The Genesis Of Retinal Horizontal Cells

Investigative Ophthalmology & Visual Science, Mar 26, 2012

Research paper thumbnail of Preclinical evaluation of photodynamic therapy to inhibit lens epithelial proliferation

Research paper thumbnail of Progressive Lipidome Changes During Retinal Degeneration in a Rat Model of Smith-Lemli-Opitz Syndrome

Investigative Ophthalmology & Visual Science, May 10, 2007

Research paper thumbnail of Visual Function in a Mouse Mutant Lacking Rod-Specific G-Protein Gamma Subunit

Research paper thumbnail of A Novel Fully Humanized RHO adRP Mouse Model

Investigative Ophthalmology & Visual Science, Apr 17, 2010

Research paper thumbnail of EDITOR’S PERSPECTIVE: On the verge of translation: Combined cholesterol-antioxidant supplementation as a potential therapeutic intervention for Smith-Lemli-Opitz syndrome

Experimental Eye Research, 2021

Research paper thumbnail of Effects of Combined Antioxidant/Cholesterol Supplementation in a Rat Model of Smith-Lemli-Opitz Syndrome

Investigative Ophthalmology & Visual Science, Apr 17, 2010

Research paper thumbnail of Aquaporin 0 Is Crucial for Proper Synapse Formation Between Cones and on Cone Bipolar Cells

Investigative Ophthalmology & Visual Science, May 14, 2008

Research paper thumbnail of Rhodopsin Resists Oxidative Modification by PUFA–Derived Aldehydes and Nitrosylation During Light– and Metabolically–Induced Retinal Degenerations

Investigative Ophthalmology & Visual Science, May 1, 2006

Research paper thumbnail of Targeting the RPE: A Novel Application for Compacted-DNA Nanoparticles

Investigative Ophthalmology & Visual Science, May 14, 2008

Research paper thumbnail of Contributors to Volume 15

Research paper thumbnail of Age–Dependent Alterations in Rod Outer Segment Membrane Properties in a Rodent Model of Smith–Lemli–Opitz Syndrome

Investigative Ophthalmology & Visual Science, May 1, 2006

Research paper thumbnail of EDITORIAL: Special issue on the role of lipid and protein oxidation in retinal degenerations

Experimental Eye Research, Apr 1, 2019

Research paper thumbnail of Background Modifier Gene Influence on Retinal Degenerations: The Effect of Apoe Isoform Expression on Rds Phenotype Characteristics

Investigative Ophthalmology & Visual Science, May 14, 2008

Research paper thumbnail of The Role of Rds Oligomerization in Cone Outer Segment Assembly and Maintenance

Investigative Ophthalmology & Visual Science, May 10, 2007

Research paper thumbnail of Dependence of visual and cognitive outcomes on animal holder configuration in a rodent model of blast overpressure exposure

Vision Research, Nov 1, 2021

Blast-induced traumatic brain injury is the signature injury of modern military conflicts. To mor... more Blast-induced traumatic brain injury is the signature injury of modern military conflicts. To more fully understand the effects of blast exposure, we placed rats in different holder configurations, exposed them to blast overpressure, and assessed the degree of eye and brain injury. Anesthetized Long-Evans rats received blast exposures directed at the head (63 kPa, 195 dB-SPL) in either an "open holder" (head and neck exposed; n = 7), or an "enclosed holder" (window for blast exposure to eye; n = 15) and were compared to non-blast exposed (control) rats (n = 22). Outcomes included optomotor response (OMR), electroretinography (ERG), and spectral domain optical coherence tomography (SD-OCT) at 2, 4, and 6 months post-blast, and cognitive function (Y-maze) at 3 months. Spatial frequency and contrast sensitivity were reduced in ipsilateral blast-exposed eyes in both holders (p < 0.01), while contralateral eyes showed greater deficits with the enclosed holder (p < 0.05). Thinner retinas (p < 0.001) and reduced ERG a- and b- wave amplitudes (p < 0.05) were observed for both ipsilateral and contralateral eyes with the enclosed, but not the open, holder. Rats in the open holder showed cognitive deficits compared to rats in the enclosed holder (p < 0.05). Overall, the animal holder configuration used in blast exposure studies can significantly affect outcomes. Enclosed holders may cause secondary damage to the contralateral eye by concussive injury or blast wave reflection off the holder wall. Open holders may damage the brain via rapid head movement (contrecoup injury). These results highlight additional factors to be considered when evaluating patients with blast exposure or developing models of blast injury.

Research paper thumbnail of A Dpagt1 Missense Variant Causes Degenerative Retinopathy without Myasthenic Syndrome in Mice

International Journal of Molecular Sciences, Oct 9, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of A <i>Dpagt1</i> Missense Variant Causes Early Degenerative Retinopathy without Myasthenic Syndrome in Mice

Congenital Disorders of Glycosylation (CDG) are a heterogenous group of primarily autosomal reces... more Congenital Disorders of Glycosylation (CDG) are a heterogenous group of primarily autosomal recessive mendelian diseases caused by disruptions in the synthesis of lipid linked oligosaccharides and their transfer to proteins. CDGs affect multiple organ systems and vary in presentation, even within families. Here we describe a chemically induced mouse mutant, tvrm76, with early onset photoreceptor degeneration. The recessive mutation was mapped to Chromosome 9 and associated with a missense mutation in the Dpagt1 gene encoding UDP-N-acetyl-D-glucosamine:dolichyl-phosphate N-acetyl-D-glucosaminephosphotransferase (EC 2.7.8.15). The mutation is predicted to cause a substitution of aspartic acid with glycine at residue 166 of DPAGT1. Increased expression of Ddit3, and elevated levels of HSPA5 (BiP) suggest the presence of early-onset endoplasmic reticulum (ER) stress. These changes were associated with induction of photoreceptor apoptosis in tvrm76 retinas. Mutations in human DPAGT1 cause Myasthenic Syndrome 13 and severe forms of Congenital Disorder of Glycosylation Type Ij. In contrast, Dpagt1 tvrm76 homozygous mice present with congenital photoreceptor degeneration without overt muscle or muscular junction involvement. Our results suggest the possibility of DPAGT1 mutations in human patients that present primarily with retinitis pigmentosa with little or no muscle disease. Variants in DPAGT1 should be considered when evaluating cases of non-syndromic retinal degeneration.

Research paper thumbnail of The subretinal drusenoid deposit (SDD) of age-related macular degeneration (AMD) may have a specific and strong association with high-risk vascular diseases (HRVDs)

Research paper thumbnail of Chemistry and metabolism of lipids in the vertebrate retina

Progress in Lipid Research, 1983

I. INTRODUCTION II. CELLULAR ORGANIZATION OF THE VERTEBRATE RETINA II1. STRUCTURAL ORGANIZATION O... more I. INTRODUCTION II. CELLULAR ORGANIZATION OF THE VERTEBRATE RETINA II1. STRUCTURAL ORGANIZATION OF VERTEBRATE PHOTORECEPTOR CELLS IV. LIPID COMPOSITION OF THE VERTEBRATE RETINA A. Historical considerations and general composition B. Phospholipid class composition C. Fatty acid composition D. Neutral lipids E. Glycolipids and other polar lipids V. LIPID COMPOSITION OF VERTEBRATE PHOTORECEPTOR OUTER SEGMENT MEMBRANES A. Preparation B. General composition C. Lipid class composition I. Phospholipids 2. Neutral lipids D. Fatty acid composition and phospholipid molecular species E. Molecular organization of lipids in rod outer segment disc membranes VI. LIPID METABOLISM IN THE VERTEBRATE RETINA A. Glyceride biosynthesis B. Fatty acids biosynthesis C. Ganglioside biosynthesis D. Sterol biosynthesis E. Phospholipid transfer proteins F. Base exchange reactions VII. LIPID METABOLISM 1N THE VERTEBRATE PHOTORECEPTOR CELLS A. Renewal and turnover of photoreceptor outer segment membranes 1. Renewal mechanisms 2. Proteins 3. Lipids B. Decarboxylation of phosphatidylserine to phosphatidylethanolamine C. Transmethylation of phosphatidylethanolamine to phosphatidylcholine VIII. EFFECT OF LIGHT ON THE METABOLISM OF RETINAL LIPIDS A. Gangliosides B. Phospholipids (other than inositides) C. Inositol phosphatides IX. THE IMPORTANCE OF LIP1DS IN NORMAL RETINA FUNCTION A. Lateral and rotational mobility of rhodopsin B. Rhodopsin orientation C. Rhodopsin regeneration and spectroscopic properties D. Thermal stability of rhodopsin E. Photobleaching of rhodopsin F. Effects of dietary manipulations on lipids of the retina X. ROLE OF LIPID PEROXIDATION IN RETINAL DEGENERATION A. Morphological changes in retinas exposed to pro-oxidant conditions B. Evidence for lipid peroxide accumulation in retinal degeneration C. Functional changes related to retinal lipid peroxides XI. CONCLUSIONS AND PERSPECTIVES

Research paper thumbnail of Onecut 1 Is Essential For The Genesis Of Retinal Horizontal Cells

Investigative Ophthalmology & Visual Science, Mar 26, 2012

Research paper thumbnail of Preclinical evaluation of photodynamic therapy to inhibit lens epithelial proliferation

Research paper thumbnail of Progressive Lipidome Changes During Retinal Degeneration in a Rat Model of Smith-Lemli-Opitz Syndrome

Investigative Ophthalmology & Visual Science, May 10, 2007

Research paper thumbnail of Visual Function in a Mouse Mutant Lacking Rod-Specific G-Protein Gamma Subunit

Research paper thumbnail of A Novel Fully Humanized RHO adRP Mouse Model

Investigative Ophthalmology & Visual Science, Apr 17, 2010

Research paper thumbnail of EDITOR’S PERSPECTIVE: On the verge of translation: Combined cholesterol-antioxidant supplementation as a potential therapeutic intervention for Smith-Lemli-Opitz syndrome

Experimental Eye Research, 2021

Research paper thumbnail of Effects of Combined Antioxidant/Cholesterol Supplementation in a Rat Model of Smith-Lemli-Opitz Syndrome

Investigative Ophthalmology & Visual Science, Apr 17, 2010

Research paper thumbnail of Aquaporin 0 Is Crucial for Proper Synapse Formation Between Cones and on Cone Bipolar Cells

Investigative Ophthalmology & Visual Science, May 14, 2008

Research paper thumbnail of Rhodopsin Resists Oxidative Modification by PUFA–Derived Aldehydes and Nitrosylation During Light– and Metabolically–Induced Retinal Degenerations

Investigative Ophthalmology & Visual Science, May 1, 2006

Research paper thumbnail of Targeting the RPE: A Novel Application for Compacted-DNA Nanoparticles

Investigative Ophthalmology & Visual Science, May 14, 2008

Research paper thumbnail of Contributors to Volume 15

Research paper thumbnail of Age–Dependent Alterations in Rod Outer Segment Membrane Properties in a Rodent Model of Smith–Lemli–Opitz Syndrome

Investigative Ophthalmology & Visual Science, May 1, 2006

Research paper thumbnail of EDITORIAL: Special issue on the role of lipid and protein oxidation in retinal degenerations

Experimental Eye Research, Apr 1, 2019

Research paper thumbnail of Background Modifier Gene Influence on Retinal Degenerations: The Effect of Apoe Isoform Expression on Rds Phenotype Characteristics

Investigative Ophthalmology & Visual Science, May 14, 2008

Research paper thumbnail of The Role of Rds Oligomerization in Cone Outer Segment Assembly and Maintenance

Investigative Ophthalmology & Visual Science, May 10, 2007

Research paper thumbnail of Dependence of visual and cognitive outcomes on animal holder configuration in a rodent model of blast overpressure exposure

Vision Research, Nov 1, 2021

Blast-induced traumatic brain injury is the signature injury of modern military conflicts. To mor... more Blast-induced traumatic brain injury is the signature injury of modern military conflicts. To more fully understand the effects of blast exposure, we placed rats in different holder configurations, exposed them to blast overpressure, and assessed the degree of eye and brain injury. Anesthetized Long-Evans rats received blast exposures directed at the head (63 kPa, 195 dB-SPL) in either an "open holder" (head and neck exposed; n = 7), or an "enclosed holder" (window for blast exposure to eye; n = 15) and were compared to non-blast exposed (control) rats (n = 22). Outcomes included optomotor response (OMR), electroretinography (ERG), and spectral domain optical coherence tomography (SD-OCT) at 2, 4, and 6 months post-blast, and cognitive function (Y-maze) at 3 months. Spatial frequency and contrast sensitivity were reduced in ipsilateral blast-exposed eyes in both holders (p < 0.01), while contralateral eyes showed greater deficits with the enclosed holder (p < 0.05). Thinner retinas (p < 0.001) and reduced ERG a- and b- wave amplitudes (p < 0.05) were observed for both ipsilateral and contralateral eyes with the enclosed, but not the open, holder. Rats in the open holder showed cognitive deficits compared to rats in the enclosed holder (p < 0.05). Overall, the animal holder configuration used in blast exposure studies can significantly affect outcomes. Enclosed holders may cause secondary damage to the contralateral eye by concussive injury or blast wave reflection off the holder wall. Open holders may damage the brain via rapid head movement (contrecoup injury). These results highlight additional factors to be considered when evaluating patients with blast exposure or developing models of blast injury.

Research paper thumbnail of A Dpagt1 Missense Variant Causes Degenerative Retinopathy without Myasthenic Syndrome in Mice

International Journal of Molecular Sciences, Oct 9, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of A <i>Dpagt1</i> Missense Variant Causes Early Degenerative Retinopathy without Myasthenic Syndrome in Mice

Congenital Disorders of Glycosylation (CDG) are a heterogenous group of primarily autosomal reces... more Congenital Disorders of Glycosylation (CDG) are a heterogenous group of primarily autosomal recessive mendelian diseases caused by disruptions in the synthesis of lipid linked oligosaccharides and their transfer to proteins. CDGs affect multiple organ systems and vary in presentation, even within families. Here we describe a chemically induced mouse mutant, tvrm76, with early onset photoreceptor degeneration. The recessive mutation was mapped to Chromosome 9 and associated with a missense mutation in the Dpagt1 gene encoding UDP-N-acetyl-D-glucosamine:dolichyl-phosphate N-acetyl-D-glucosaminephosphotransferase (EC 2.7.8.15). The mutation is predicted to cause a substitution of aspartic acid with glycine at residue 166 of DPAGT1. Increased expression of Ddit3, and elevated levels of HSPA5 (BiP) suggest the presence of early-onset endoplasmic reticulum (ER) stress. These changes were associated with induction of photoreceptor apoptosis in tvrm76 retinas. Mutations in human DPAGT1 cause Myasthenic Syndrome 13 and severe forms of Congenital Disorder of Glycosylation Type Ij. In contrast, Dpagt1 tvrm76 homozygous mice present with congenital photoreceptor degeneration without overt muscle or muscular junction involvement. Our results suggest the possibility of DPAGT1 mutations in human patients that present primarily with retinitis pigmentosa with little or no muscle disease. Variants in DPAGT1 should be considered when evaluating cases of non-syndromic retinal degeneration.