Robert Mullins, MS, PhD
Introduction
Our laboratory's primary research interests revolve around the structural and molecular basis for degenerative diseases of the retina, with particular focus on the retinal pigment epithelium in Best disease and the choriocapillaris in age-related macular degeneration. Best disease is a relatively rare but potentially devastating form of macular degeneration. Over one hundred different mutations in the responsible gene, VMD2/bestrophin, can result in this autosomal dominant disorder. Bestrophin most likely functions as a chloride channel and thus may regulate the ionic milieu in the subretinal space. We are using both in situ approaches and in vitro approaches to understand how specific mutations affect behavior of the mutant protein and to examine the regional distribution of the bestrophin protein in normal eyes, as well as to evaluate genotype-phenotype relationships for eyes with Best disease. Age-related macular degeneration (AMD) is a common cause of blindness that affects as many as one in three elderly individuals to some degree. With the increasing median age of the population, it is widely appreciated that the impact of AMD will worsen in the coming years. Recent genetic and histopathologic studies indicate that AMD is associated with inflammation, and there is strong evidence for leukocyte extravasation in the pathogenesis of the disease; however the role of the vasculature in recruiting leukocytes during these inflammatory events is poorly understood. The choriocapillaris is the capillary bed responsible for nourishing the photoreceptor cells of the retina, and is the most likely source for recruiting leukocytes in AMD. We are interested in determining the biological changes of the choriocapillaris in eyes with macular degeneration by examining human donor tissue, as well as cell surface molecules that differ between normal and neovascular endothelial cells. In addition to ?descriptive? studies in situ, we are interested in characterizing the molecular responses of human choroidal endothelial cells (cultured from human eyes) to the types of microenvironmental pro-inflammatory challenges that occur in macular degeneration, including exposure to complement components and products of extracellular matrix protein degradation. Molecular and functional assays of human choroidal EC are performed in the presence or absence of these ?AMD microenvironment? challenges. In addition we have several active collaborations in The University of Iowa, evaluating animal models of inherited retinal diseases, and assisting other faculty in answering histological questions in the eye.
Current Positions
- Professor of Ophthalmology and Visual Sciences
- Martin Carver Chair in Ocular Cell Biology
Education
- BS in Biology, Wheaton College, Wheaton, Illinois, United States
- MS in Biology, Saint Louis University, St. Louis, Missouri, United States
- PhD in Cell and Molecular Biology, Saint Louis University, St. Louis, Missouri, United States
- Postdoctoral Fellow in Postdoctoral Fellow, Center on Aging, The University of Iowa, Iowa City, Iowa, United States
Graduate Program Affiliations
Center, Program and Institute Affiliations
Research Interests
- The role of the complement system in age-related macular degeneration
- Cell biology of inherited maculopathies
- Our laboratory's primary research interests revolve around the structural and molecular basis for degenerative diseases of the retina, with particular focus on the retinal pigment epithelium in Best disease and the choriocapillaris in age-related macular degeneration. Best disease is a relatively rare but potentially devastating form of macular degeneration. Over one hundred different mutations in the responsible gene, VMD2/bestrophin, can result in this autosomal dominant disorder. Bestrophin most likely functions as a chloride channel and thus may regulate the ionic milieu in the subretinal space. We are using both in situ approaches and in vitro approaches to understand how specific mutations affect behavior of the mutant protein and to examine the regional distribution of the bestrophin protein in normal eyes, as well as to evaluate genotype-phenotype relationships for eyes with Best disease. Age-related macular degeneration (AMD) is a common cause of blindness that affects as many as one in three elderly individuals to some degree. With the increasing median age of the population, it is widely appreciated that the impact of AMD will worsen in the coming years. Recent genetic and histopathologic studies indicate that AMD is associated with inflammation, and there is strong evidence for leukocyte extravasation in the pathogenesis of the disease; however the role of the vasculature in recruiting leukocytes during these inflammatory events is poorly understood. The choriocapillaris is the capillary bed responsible for nourishing the photoreceptor cells of the retina, and is the most likely source for recruiting leukocytes in AMD. We are interested in determining the biological changes of the choriocapillaris in eyes with macular degeneration by examining human donor tissue, as well as cell surface molecules that differ between normal and neovascular endothelial cells. In addition to ?descriptive? studies in situ, we are interested in characterizing the molecular responses of human choroidal endothelial cells (cultured from human eyes) to the types of microenvironmental pro-inflammatory challenges that occur in macular degeneration, including exposure to complement components and products of extracellular matrix protein degradation. Molecular and functional assays of human choroidal EC are performed in the presence or absence of these ?AMD microenvironment? challenges. In addition we have several active collaborations in The University of Iowa, evaluating animal models of inherited retinal diseases, and assisting other faculty in answering histological questions in the eye.
- Endothelial cell activation and dysfunction in macular degeneration
- Extracellular matrix abnormalities in aging and ocular pathology
- Modeling retinal diseases in vitro and in vivo
- Animal models for central serous retinopathy and other retinal diseases
- Choroidal endothelial cell activation and dysfunction in macular degeneration
- Mechanism(s) of Best disease
Selected Publications
- Sekulic A, Herr SM, Mulfaul K, Pompös IM, Winkler S, Dietrich C, Obermayer B, Mullins RF, Conrad T, Zipfel PF, Sennlaub F, Skerka C, Strauß O. (2025). Factor-H-related protein 1 (FHR1), a promotor of para-inflammation in age-related macular degeneration. J Neuroinflammation 22(1):173. DOI: 10.1186/s12974-025-03499-z. PMID: 40611130. PMCID: PMC12226897.
- Stone NE, Bohrer LR, Mullin NK, Berthold A, Wright AT, Han IC, Stone EM, Mullins RF, Tucker BA. (2025). Device-free isolation of photoreceptor cells from patient iPSC-derived retinal organoids. JCI Insight 12:e186338. ONLINE AHEAD OF PRINT. DOI: 10.1172/jci.insight.186338. PMID: 40504625.
- Sekulic A, Pompos IM, Perie L, Winkler S, Mulfaul K, Mullins RF, Sennlaub F, Zipfel PF, Skerka C, Strauss O. (2024). Role of Factor H Related Protein 1 in Age Related Macular Degeneration. European Journal of Immunology 54(s:2):167-168.
- Mullin NK, Bohrer LR, Voigt AP, Lozano LP, Wright AT, Bonilha VL, Mullins RF, Stone EM, Tucker BA. (2024). NR2E3 loss disrupts photoreceptor cell maturation and fate in human organoid models of retinal development. J Clin Invest 134(11):e173892. DOI: 10.1172/JCI173892. PMID: 38652563. PMCID: PMC11142732.
- Burnight ER, Fenner BJ, Han IC, DeLuca AP, Whitmore SS, Bohrer LR, Andorf JL, Sohn EH, Mullins RF, Tucker BA, Stone EM. (2024). Demonstration of the pathogenicity of a common non-exomic mutation in ABCA4 using iPSC-derived retinal organoids and retrospective clinical data. Hum Mol Genet 33(16):1379-1390. DOI: 10.1093/hmg/ddad176. PMID: 37930186. PMCID: PMC11305681.
- Edwards MM, Mullins RF. (2025). Editorial: In memory of Jerry Lutty. Experimental Eye Research 251:110226. DOI: 10.1016/j.exer.2024.110226. PMID: 39736314.
- Tucker BA, Burnight ER, Cranston CM, Ulferts MJ, Luse MA, Westfall T, Scott CA, Marsden A, Gibson-Corley K, Wiley LA, Han IC, Slusarski DC, Mullins RF, Stone EM. (2022). Development and biological characterization of a clinical gene transfer vector for the treatment of MAK-associated retinitis pigmentosa. Gene Ther 29(5):259-288. DOI: 10.1038/s41434-021-00291-5. PMID: 34518651. PMCID: PMC9159943.
- Han IC, Wiley LA, Ochoa D, Lang MJ, Harman BE, Sheehan KM, Mullins RF, Stone EM, Tucker BA. (2023). Characterization of a novel Pde6b-deficient rat model of retinal degeneration and treatment with adeno-associated virus (AAV) gene therapy. Gene Ther. Apr;30(3-4):362-368. DOI: 10.1038/s41434-022-00365-y. PMID: 36175490.
- Wiley LA, Boyce TM, Meyering EE, Ochoa D, Sheehan KM, Stone EM, Mullins RF, Tucker BA, Han IC. (2023). The Degree of Adeno-Associated Virus-Induced Retinal Inflammation Varies Based on Serotype and Route of Delivery: Intravitreal, Subretinal, or Suprachoroidal. Hum Gene Ther 34(11-12):530-539. DOI: 10.1089/hum.2022.222. PMID: 36793189. PMCID: PMC10282814.
- Burnight ER, Wiley LA, Mullin NK, Adur MK, Lang MJ, Cranston CM, Jiao C, Russell SR, Sohn EH, Han IC, Ross JW, Stone EM, Mullins RF, Tucker BA. (2023). CRISPRi-Mediated Treatment of Dominant Rhodopsin-Associated Retinitis Pigmentosa. CRISPR J 6(6):502-513. DOI: 10.1089/crispr.2023.0039. PMID: 38108516. PMCID: PMC11304754.