Paul A. Sieving
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View article: Addressing Challenges in Developing Treatments for Inherited Retinal Diseases: Recommendations From the Third Monaciano Symposium
Addressing Challenges in Developing Treatments for Inherited Retinal Diseases: Recommendations From the Third Monaciano Symposium Open
Over the past decade, efforts focused on developing genetic therapies for inherited retinal diseases have advanced steadily to clinical trials and the development of a treatment, fueling optimism for the potential of precision medicines to…
View article: Dark Rearing Does Not Alter Developmental Retinoschisis Cavity Formation in Rs1 Gene Knockout Rat Model of X-Linked Retinoschisis
Dark Rearing Does Not Alter Developmental Retinoschisis Cavity Formation in Rs1 Gene Knockout Rat Model of X-Linked Retinoschisis Open
Background/Objective: The Rs1 exon-1-del rat (Rs1KO) XLRS model shows normal retinal development until postnatal day 12 (P12) when small cystic spaces start to form in the inner nuclear layer. These enlarge rapidly, peak at P15, and then c…
View article: Ocular Phenotyping of Knockout Mice Identifies Genes Associated With Late Adult Retinal Phenotypes
Ocular Phenotyping of Knockout Mice Identifies Genes Associated With Late Adult Retinal Phenotypes Open
We identified 12 mouse genes with significant late-adult abnormal retinal pathology, eight of which have not been previously implicated in either mouse or human retinal physiology or pathology. These serve as novel retinal disease gene can…
View article: Kir4.1 and Aqp4 Contribution to Schisis Cystic Water Accumulation and Clearance in the Rs1 Exon-1 Del XLRS Rat Model
Kir4.1 and Aqp4 Contribution to Schisis Cystic Water Accumulation and Clearance in the Rs1 Exon-1 Del XLRS Rat Model Open
Background/Objective: The Rs1 exon-1-del rat (Rs1KO) XLRS model shows normal retinal development until postnatal day 12 (P12) when small cystic spaces start to form in the inner nuclear layer. These spaces enlarge rapidly, peak at P15, and…
View article: OCT Intensity of the Region between Outer Retina Band 2 and Band 3 as a Biomarker for Retinal Degeneration and Therapy
OCT Intensity of the Region between Outer Retina Band 2 and Band 3 as a Biomarker for Retinal Degeneration and Therapy Open
Optical coherence tomography (OCT) is widely used to probe retinal structure and function. This study investigated the outer retina band (ORB) pattern and reflective intensity for the region between bands 2 and 3 (Dip) in three mouse model…
View article: Statistical Evaluation of ERG Responses: A New Method to Validate Cycle-by-Cycle Recordings in Advanced Retinal Degenerations
Statistical Evaluation of ERG Responses: A New Method to Validate Cycle-by-Cycle Recordings in Advanced Retinal Degenerations Open
This novel method extracts highly reliable clinical recordings of low-amplitude flicker ERGs and effectively detects artifactual responses. It has potential value both as a cone outcome variable and planning tool in clinical trials on natu…
View article: A Spontaneous Nonhuman Primate Model of Myopic Foveoschisis
A Spontaneous Nonhuman Primate Model of Myopic Foveoschisis Open
This nonhuman primate model of foveoschisis reveals insights into how acquired myopic traction leads to phenotypically similar morphologic and cellular changes as congenital XLRS without alterations in RS1.
View article: X-Linked Retinoschisis
X-Linked Retinoschisis Open
X-linked retinoschisis (XLRS) is an inherited vitreoretinal dystrophy causing visual impairment in males starting at a young age with an estimated prevalence of 1:5000 to 1:25,000. The condition was first observed in two affected brothers …
View article: XLRS Rat with Rs1-/Y Exon-1-Del Shows Failure of Early Postnatal Outer Retina Development
XLRS Rat with Rs1-/Y Exon-1-Del Shows Failure of Early Postnatal Outer Retina Development Open
We generated a Long Evans transgenic rat with targeted deletion of the whole Rs1 exon-1 and evaluated the pathological retinal phenotype of this Rs1-/Y rat model of X-linked retinoschisis (XLRS). The Rs1−/Y rat exhibited very early onset a…
View article: Ethical considerations regarding animal experimentation
Ethical considerations regarding animal experimentation Open
Animal experimentation is widely used around the world for the identification of the root causes of various diseases in humans and animals and for exploring treatment options. Among the several animal species, rats, mice and purpose-bred b…
View article: Methodology for clinical research
Methodology for clinical research Open
A clinical research requires a systematic approach with diligent planning, execution and sampling in order to obtain reliable and validated results, as well as an understanding of each research methodology is essential for researchers. Ind…
View article: Targeted Expression of Retinoschisin by Retinal Bipolar Cells in XLRS Promotes Resolution of Retinoschisis Cysts Sans RS1 From Photoreceptors
Targeted Expression of Retinoschisin by Retinal Bipolar Cells in XLRS Promotes Resolution of Retinoschisis Cysts Sans RS1 From Photoreceptors Open
These results demonstrate that RS1 gene expression primarily in bipolar cells of the XLRS mouse retina, independent of photoreceptor expression, can ameliorate retinoschisis structural pathology and provide further evidence of RS1 role in …
View article: Predominant Founder Effect among Recurrent Pathogenic Variants for an X-Linked Disorder
Predominant Founder Effect among Recurrent Pathogenic Variants for an X-Linked Disorder Open
For disorders with X-linked inheritance, variants may be transmitted through multiple generations of carrier females before an affected male is ascertained. Pathogenic RS1 variants exclusively cause X-linked retinoschisis (XLRS). While RS1…
View article: Comprehensive variant spectrum of the <i>CNGA3</i> gene in patients affected by achromatopsia
Comprehensive variant spectrum of the <i>CNGA3</i> gene in patients affected by achromatopsia Open
Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by impaired color discrimination, low visual acuity, photosensitivity, and nystagmus. To date, six genes have been associated with ACHM (CNGA3, CNGB3, GNAT2, PD…
View article: AMPK modulation ameliorates dominant disease phenotypes of CTRP5 variant in retinal degeneration
AMPK modulation ameliorates dominant disease phenotypes of CTRP5 variant in retinal degeneration Open
Late-onset retinal degeneration (L-ORD) is an autosomal dominant disorder caused by a missense substitution in CTRP5 . Distinctive clinical features include sub-retinal pigment epithelium (RPE) deposits, choroidal neovascularization, and R…
View article: Deciphering the genetic architecture and ethnographic distribution of IRD in three ethnic populations by whole genome sequence analysis
Deciphering the genetic architecture and ethnographic distribution of IRD in three ethnic populations by whole genome sequence analysis Open
Patients with inherited retinal dystrophies (IRDs) were recruited from two understudied populations: Mexico and Pakistan as well as a third well-studied population of European Americans to define the genetic architecture of IRD by performi…
View article: Rs1h−/y exon 3-del rat model of X-linked retinoschisis with early onset and rapid phenotype is rescued by RS1 supplementation
Rs1h−/y exon 3-del rat model of X-linked retinoschisis with early onset and rapid phenotype is rescued by RS1 supplementation Open
Animal models of X-linked juvenile retinoschisis (XLRS) are valuable tools for understanding basic biochemical function of retinoschisin (RS1) protein and to investigate outcomes of preclinical efficacy and toxicity studies. In order to wo…
View article: MASSIVE ADVANCING NONEXUDATIVE TYPE 1 CHOROIDAL NEOVASCULARIZATION IN CTRP5 LATE-ONSET RETINAL DEGENERATION
MASSIVE ADVANCING NONEXUDATIVE TYPE 1 CHOROIDAL NEOVASCULARIZATION IN CTRP5 LATE-ONSET RETINAL DEGENERATION Open
Purpose: To describe longitudinal multimodal imaging findings of nonexudative choroidal neovascularization in CTRP5 late-onset retinal degeneration. Methods: Four patients with CTRP5-positive late-onset retinal degeneration underwent repea…
View article: Host Immune Responses after Suprachoroidal Delivery of AAV8 in Nonhuman Primate Eyes
Host Immune Responses after Suprachoroidal Delivery of AAV8 in Nonhuman Primate Eyes Open
The suprachoroid is a potential space located between the sclera and choroid of the eye, which provides a novel route for ocular drug or viral vector delivery. Suprachoroidal injection of adeno-associated virus (AAV)8 using transscleral mi…
View article: Genetic Rescue of X-Linked Retinoschisis Mouse ( <i>Rs1</i> <sup>−/y</sup> ) Retina Induces Quiescence of the Retinal Microglial Inflammatory State Following AAV8- <i>RS1</i> Gene Transfer and Identifies Gene Networks Underlying Retinal Recovery
Genetic Rescue of X-Linked Retinoschisis Mouse ( <i>Rs1</i> <sup>−/y</sup> ) Retina Induces Quiescence of the Retinal Microglial Inflammatory State Following AAV8- <i>RS1</i> Gene Transfer and Identifies Gene Networks Underlying Retinal Recovery Open
To understand RS1 gene interaction networks in the X-linked retinoschisis (XLRS) mouse retina (Rs1-/y), we analyzed the transcriptome by RNA sequencing before and after in vivo expression of exogenous retinoschisin (RS1) gene delivered by …
View article: Host immune responses after suprachoroidal delivery of AAV8 in nonhuman primate eyes
Host immune responses after suprachoroidal delivery of AAV8 in nonhuman primate eyes Open
The suprachoroid is a potential space located between the sclera and choroid of the eye which provides a novel route for ocular drug or viral vector delivery. Suprachoroidal injection of AAV8 using transscleral microneedles enables widespr…
View article: NEI-Supported Age-Related Macular Degeneration Research: Past, Present, and Future
NEI-Supported Age-Related Macular Degeneration Research: Past, Present, and Future Open
NEI now stands poised to expand the resources available to clinical investigators to uncover disease mechanisms and move experimental therapies into clinical trials.
View article: Trans-Ocular Electric Current In Vivo Enhances AAV-Mediated Retinal Transduction in Large Animal Eye After Intravitreal Vector Administration
Trans-Ocular Electric Current In Vivo Enhances AAV-Mediated Retinal Transduction in Large Animal Eye After Intravitreal Vector Administration Open
This work has potential translational relevance to human ocular gene therapy by increasing retinal expression of therapeutic vectors given by intravitreal administration.
View article: Advancing Clinical Trials for Inherited Retinal Diseases: Recommendations from the Second Monaciano Symposium
Advancing Clinical Trials for Inherited Retinal Diseases: Recommendations from the Second Monaciano Symposium Open
Major advances in the study of inherited retinal diseases (IRDs) have placed efforts to develop treatments for these blinding conditions at the forefront of the emerging field of precision medicine. As a result, the growth of clinical tria…