About

Catherine Bowes Rickman is the George and Geneva Boguslavsky Distinguished Professor of Eye Research, a Professor of Ophthalmology, and a Professor in Cell Biology at Duke University. She is based at the 5010 Albert Eye Research Institute in Durham, North Carolina. Her academic roles include positions within the Program in Cell and Molecular Biology, the Developmental & Stem Cell Biology Program, and the Third Year University Program in Genetics and Genomics. Her research focuses on eye research, with a particular emphasis on cellular and molecular mechanisms related to ophthalmology. She is involved in advanced research initiatives at Duke, contributing to the fields of eye health and molecular biology.

Research topics

• Biology
• Cell biology
• Medicine
• Genetics
• Biochemistry
• Chemistry
• Neuroscience
• Internal medicine
• Biophysics
• Ophthalmology
• Immunology
• Pathology

Selected publications

• Optimized Minimally Invasive Transscleral Subretinal Injection Technique in Mouse

  Journal of Visualized Experiments · 2025-07-25

  article

  The conventional method of material delivery to the subretinal space in the mouse involves dual perforation of the neural retina, which causes extensive surgical damage. This leads to variability in the subsequent outcome measures of the visual function, such as electroretinogram (ERG) recordings or behavioral vision assays, which confound efficacy assessments of experimental therapeutics. To overcome these barriers, we optimized a transscleral minimally invasive subretinal injection technique in mice. In this technique, the superior fornix is accessed using a custom-made tungsten wire eyelid speculum to perform conjunctival peritomy and tenotomy. A pinpoint sclerotomy is made using a diamond knife without penetrating the retina, through which a fine glass needle is carefully inserted at a shallow angle. The payload is delivered to the subretinal space using a microinjection pump. Optical coherence tomography (OCT) is used to assess the size and position of the subretinal bleb immediately following injection. We compared the outcomes of this technique to the conventional transretinal method performed using a spring-loaded syringe with a 33G needle sclerotomy. ERG recordings indicated excellent preservation of retinal function in transsclerally-injected mice, comparable to that of uninjected control mice. In contrast, an appreciable ERG signal reduction was observed in the conventionally injected cohorts. In summary, we have optimized a minimally invasive technique for subretinal injection in mice. We demonstrate that this technique is a robust and efficient method for gene therapy administration that minimizes anatomic damage to the retina and has minimal impact on retinal function. This method lowers the threshold for the development of therapies targeting both the retinal pigmented epithelium and photoreceptors to treat a wide range of retinal and macular diseases.

  PublisherDOI

• Truncated complement factor H Y402 gene therapy rescues C3 glomerulonephritis

  Molecular Therapy · 2025-04-24 · 1 citations

  articleOpen accessSenior author

  mouse model of C3G. We tested three different tCFH vectors and found significant differences in their relative transduction efficiency and therapeutic efficacy. These discoveries motivate the development of AAV-mediated tCFH replacement therapy for patients with C3G while simultaneously demonstrating proof of concept for AAV-mediated tCFH gene augmentation therapy for patients with AMD.

  PublisherDOI

• Reprogramming Factors Activate a Non-Canonical Oxidative Resilience Pathway That Can Rejuvenate RPEs and Restore Vision

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-01

  preprintOpen access

  Oct4, Sox2, and Klf4 (OSK) Yamanaka factors induce pluripotency and reverse age-related epigenetic changes, yet the mechanisms by which they promote rejuvenation remain poorly explored. Oxidative stress contributes to CNS aging and retinal pigmented epithelium (RPE) degeneration in age-related macular degeneration. We find that OSK expression in RPE restores retinal structure and visual function in aged mice and promotes oxidative resilience through a non-canonical, Tet2-independent pathway. Integrative functional genomics identifies GSTA4, a detoxifying enzyme that clears the lipid peroxidation byproduct 4-HNE, as a necessary and sufficient OSK effector. Dynamic GSTA4 regulation by OSK recapitulates a stem cell derived stress resilience program. GSTA4 overexpression alone enhances mitochondrial resilience, rejuvenates the aged RPE transcriptome, and reverses visual decline. GSTA4 is consistently upregulated across diverse lifespan-extending interventions suggesting a broader pro-longevity role. These findings uncover a previously unrecognized protective axis driven by Yamanaka factors that circumvents reprogramming, providing therapeutic insights for age-related diseases. HIGHLIGHTS: OSK-GSTA4 provides a dynamic, Tet2-independent stress-resilience axis.Functional genomics pinpoints GSTA4 as a direct downstream effector activated by OSK.RPE aging involves progressive accumulation of 4-HNE that can be detoxified by GSTA4.Enhancing GSTA4 rejuvenates RPE cells, restores vision and is associated with lifespan-extending interventions.

  PublisherOA PDFDOI

• Dissecting the biological complexity of age-related macular degeneration: Is it one disease, multiple separate diseases, or a spectrum?

  Experimental Eye Research · 2025-02-19 · 4 citations

  reviewOpen accessSenior authorCorresponding

  Clinicians recognize the heterogeneity of age-related macular degeneration (AMD) in presentation, progression, and treatment response, as well as the challenges in distinguishing it from other macular degenerations. As part of the 2024 Ryan Initiative for Macular Research meeting, a group of clinician-scientists and basic scientists were convened to consider the question of whether AMD should be classified as a single disorder or a spectrum of conditions. To answer this question, we reviewed research on several “dimensions” that constitute AMD risk or pathogenesis: genetics, ancestry, retinal imaging findings, diet and environment, aging, and outer retinal molecular and cellular pathways. The group reached a consensus that AMD represents a heterogeneous collection of disease states arising from the interplay of these dimensions. This heterogeneity can be conceived of as a “cloud” of AMD phenotypes. Defining subtypes within this “cloud” requires longitudinal cohorts of well-genotyped and phenotyped patients who progress from no AMD through late AMD, analyzed by unsupervised learning. Comparing the AMD subtypes that emerge from this analysis, especially -omics data from each subtype, will illuminate biology that is applicable to certain subtypes of AMD patients and molecular pathogenic mechanisms that universally apply to all AMD. This knowledge will, in turn, drive improved drug development. • Rather than being a single disease, AMD is either a continuous or discontinuous spectrum with varying presentations, progression rates, outcomes, and responses to treatment. • Multiple factors contribute to AMD, including genetics, ancestry, retinal imaging findings, diet/environment, aging, and outer retina biological pathways. • The factors that contribute to AMD can be conceived of as axes on a multi-dimensional coordinate system, with AMD occupying a cloud of points in this coordinate system. • Well-characterized longitudinal studies of AMD patients need to be combined with unsupervised learning to define disease subtypes that exist within the AMD “cloud”. • With AMD subtypes defined, comparing omics data between subtypes will identify biological pathways and therapeutic targets critical for specific AMD subtypes.

  PublisherDOI

• Small Extracellular Vesicle-Associated MiRNAs in Polarized Retinal Pigmented Epithelium

  Investigative Ophthalmology & Visual Science · 2024-11-26 · 6 citations

  articleOpen accessSenior author

  Purpose: Oxidative stress in the retinal pigmented epithelium (RPE) has been implicated in age-related macular degeneration by impacting endocytic trafficking, including the formation, content, and secretion of extracellular vesicles (EVs). Using our model of polarized primary porcine RPE (pRPE) cells under chronic subtoxic oxidative stress, we tested the hypothesis that RPE miRNAs packaged into EVs are secreted in a polarized manner and contribute to maintaining RPE homeostasis. Methods: Small EVs (sEVs) enriched for exosomes were isolated from apical and basal conditioned media from pRPE cells grown for up to four weeks with or without low concentrations of hydrogen peroxide using two sEV isolation methods, leading to eight experimental groups. The sEV miRNA expression was profiled using miRNA-Seq with Illumina MiSeq, followed by quality control and bioinformatics analysis for differential expression using the R computing environment. Expression of selected miRNAs were validated using qRT-PCR. Results: We identified miRNA content differences carried by sEVs isolated using two ultracentrifugation-based methods. Regardless of the sEV isolation method, miR-182 and miR-183 were enriched in the cargo of apically secreted sEVs, and miR-122 in the cargo of basally secreted sEVs from RPE cells during normal homeostatic conditions. After oxidative stress, miR-183 levels were significantly decreased in the cargo of apically released sEVs from stressed RPE cells. Conclusions: We curated RPE sEV miRNA datasets based on cell polarity and oxidative stress. Unbiased miRNA analysis identified differences based on polarity, stress, and sEV isolation methods. These findings suggest that miRNAs in sEVs may contribute to RPE homeostasis and function in a polarized manner.

  PublisherOA PDFDOI

• Microglia at sites of atrophy restrict the progression of retinal degeneration via galectin-3 and Trem2

  The Journal of Experimental Medicine · 2024-01-13 · 54 citations

  articleOpen access

  Outer retinal degenerations, including age-related macular degeneration (AMD), are characterized by photoreceptor and retinal pigment epithelium (RPE) atrophy. In these blinding diseases, macrophages accumulate at atrophic sites, but their ontogeny and niche specialization remain poorly understood, especially in humans. We uncovered a unique profile of microglia, marked by galectin-3 upregulation, at atrophic sites in mouse models of retinal degeneration and human AMD. In disease models, conditional deletion of galectin-3 in microglia led to phagocytosis defects and consequent augmented photoreceptor death, RPE damage, and vision loss, indicating protective roles. Mechanistically, Trem2 signaling orchestrated microglial migration to atrophic sites and induced galectin-3 expression. Moreover, pharmacologic Trem2 agonization led to heightened protection but in a galectin-3-dependent manner. In elderly human subjects, we identified this highly conserved microglial population that expressed galectin-3 and Trem2. This population was significantly enriched in the macular RPE-choroid of AMD subjects. Collectively, our findings reveal a neuroprotective population of microglia and a potential therapeutic target for mitigating retinal degeneration.

  PublisherOA PDFDOI

• Truncated Complement Factor H Y402 Gene Therapy Cures C3 Glomerulonephritis

  bioRxiv (Cold Spring Harbor Laboratory) · 2024

  Senior authorCorresponding
  • Immunology
  • Medicine
  • Biology

  -/- mouse model of C3G. While past efforts to treat C3G using exogenous human CFH resulted in limited success before immune rejection led to a foreign protein response, our findings demonstrate the capacity for long-term AAV-mediated delivery of truncated CFH (tCFH) to restore inhibition of the alternative pathway of complement and ultimately reverse C3G without immune rejection. Comparing results from the administration of several tCFH vectors also revealed significant differences in their relative efficiency and efficacy. These discoveries pave the way for subsequent development of AAV-mediated tCFH replacement therapy for patients with C3G, while simultaneously demonstrating proof of concept for a parallel AAV-mediated tCFH gene augmentation therapy for patients with AMD.

  PublisherDOI

• Aging and intraocular pressure homeostasis in mice

  Aging Cell · 2024-04-02 · 19 citations

  articleOpen access

  Age and elevated intraocular pressure (IOP) are the two primary risk factors for glaucoma, an optic neuropathy that is the leading cause of irreversible blindness. In most people, IOP is tightly regulated over a lifetime by the conventional outflow tissues. However, the mechanistic contributions of age to conventional outflow dysregulation, elevated IOP and glaucoma are unknown. To address this gap in knowledge, we studied how age affects the morphology, biomechanical properties and function of conventional outflow tissues in C57BL/6 mice, which have an outflow system similar to humans. As reported in humans, we observed that IOP in mice was maintained within a tight range over their lifespan. Remarkably, despite a constellation of age-related changes to the conventional outflow tissues that would be expected to hinder aqueous drainage and impair homeostatic function (decreased cellularity, increased pigment accumulation, increased cellular senescence and increased stiffness), outflow facility, a measure of conventional outflow tissue fluid conductivity, was stable with age. We conclude that the murine conventional outflow system has significant functional reserve in healthy eyes. However, these age-related changes, when combined with other underlying factors, such as genetic susceptibility, are expected to increase risk for ocular hypertension and glaucoma.

  PublisherOA PDFDOI

• The prion protein is required for normal responses to light stimuli by photoreceptors and bipolar cells

  iScience · 2024-09-13

  articleOpen access

  <h2>Summary</h2> The prion protein, PrP^C, is well known as an essential susceptibility factor for neurodegenerative prion diseases, yet its function in normal, healthy cells remains uncertain. A role in synaptic function has been proposed for PrP^C, supported by its cell surface expression in neurons and glia. Here, in mouse retina, we localized PrP^C to the junctions between photoreceptors and bipolar cells using synaptic proteins EAAT5, CtBP2, and PSD-95. PrP^C localized most densely with bipolar cell dendrites synapsing with cone photoreceptors. In two coisogenic mouse strains, deletion of the gene encoding PrP^C, <i>Prnp</i>, significantly altered the scotopic and/or photopic electroretinographic (ERG) responses of photoreceptors and bipolar cells. Cone-dominant pathways showed the most significant ERG changes. Retinal thickness, quantitated by high-resolution optical coherence tomography (OCT), and ribbon synapse morphology were not altered upon deletion of PrP^C, suggesting that the ERG changes were driven by functional rather than structural alterations.

  PublisherDOI

• Polarized desmosome and hemidesmosome shedding via small extracellular vesicles is an early indicator of outer blood‐retina barrier dysfunction

  Journal of Extracellular Biology · 2023-10-01 · 17 citations

  articleOpen accessCorresponding

  The retinal pigmented epithelium (RPE) constitutes the outer blood-retinal barrier, enables photoreceptor function of the eye, and is constantly exposed to oxidative stress. As such, dysfunction of the RPE underlies pathology leading to development of age-related macular degeneration (AMD), the leading cause of vision loss among the elderly in industrialized nations. A major responsibility of the RPE is to process photoreceptor outer segments, which relies on the proper functioning of its endocytic pathways and endosomal trafficking. Exosomes and other extracellular vesicles (EVs) from RPE are an essential part of these pathways and may be early indicators of cellular stress. To test the role of small EVs (sEVs) including exosomes, that may underlie the early stages of AMD, we used a polarized primary RPE cell culture model under chronic subtoxic oxidative stress. Unbiased proteomic analyses of highly purified basolateral sEVs from oxidatively stressed RPE cultures revealed changes in proteins involved in epithelial barrier integrity. There were also significant changes in proteins accumulating in the basal-side sub-RPE extracellular matrix during oxidative stress, that could be prevented with an inhibitor of sEV release. Thus, chronic subtoxic oxidative stress in primary RPE cultures induces changes in sEV content, including basal-side specific desmosome and hemidesmosome shedding via sEVs. These findings provide novel biomarkers of early cellular dysfunction and opportunity for therapeutic intervention in age-related retinal diseases (e.g., AMD).

  PublisherOA PDFDOI

Recent grants

• Complement and Pathogenic Mechanisms of AMD

  NIH · $2.3M · 2009–2015

• Innate immunity, lipoproteins and AMD progression

  NIH · $2.0M · 2016–2019

• Complement factor H modulates lipoprotein clearance in AMD

  NIH · $2.8M · 2020–2025

• Center Core Grant for Vision Research

  NIH · $16.4M · 1997–2026

• NIH Grant R01EY011286

  NIH · $2.5M · 2006

Frequent coauthors

• Una Kelly

  Duke University

  56 shared

• Jindong Ding

  Duke Medical Center

  53 shared

• Goldis Malek

  44 shared

• Mikael Klingeborn

  McLaughlin Research Institute

  37 shared

• Patrick M. Sullivan

  32 shared

• Brian E. Mace

  Duke University

  31 shared

• Peter Saloupis

  Duke University

  26 shared

• J.N. Ebright

  Duke Medical Center

  25 shared

Labs

• 5010 Albert Eye Research InstitutePI

Education

• Postdoctoral Fellowship, Ophthalmology/Jules Stein Eye Institute

  University of California, Los Angeles

  1993

• PhD, Experiemental Pathology

  University of California, Los Angeles

  1989

• B.A. Biochemistry/Molecular Biology & Aquatic Biology

  University of California, Santa Barbara

  1983

Awards & honors

• George and Geneva Boguslavsky Distinguished Professor of Eye…