About

Gregory S. Hageman, PhD, is a Distinguished Professor and the John A. Moran Presidential Professor of Ophthalmology and Visual Sciences at the University of Utah John A. Moran Eye Center. He serves as the Executive Director of Moran’s Steele Center for Translational Medicine (SCTM), which was created to exploit a repository of patient and tissue resources and foster a robust understanding of age-related macular degeneration (AMD) biology to discover pathways, identify and validate therapeutic targets, and develop therapies for early-stage AMD. Dr. Hageman's primary research interest over the past 30 years has been directed toward the genetics and biology of AMD, a leading cause of irreversible worldwide blindness. He and his colleagues discovered that a specific common haplotype of the complement regulator, Complement Factor H (CFH), in combination with variations in another complement regulator, Complement Factor B (CFB), account for greater than 50% of risk for AMD in Caucasian populations. More recently, he has generated strong ocular and systemic evidence that AMD is at least two biologically distinct diseases. Dr. Hageman has garnered contiguous funding from the National Eye Institute/National Institutes of Health for more than 25 years and was the principal investigator of a $14.7 million translational award supported by NIH/NEI involving multiple institutions. He has held academic appointments in France and the UK, and honorary professorships at Queen’s University, Belfast, and the Shandong Eye Institute, Qingdao, China. Dr. Hageman has been actively involved in various professional organizations, advisory boards, and review committees, and has briefed the U.S. Congress on three occasions. He has received numerous awards and honors for his contributions to AMD research, including the Trustee Award from the Foundation Fighting Blindness, the Alcon Research Institute Award, and the Lew R. Wasserman Merit Award, among others. Additionally, he co-founded Voyant Biotherapeutics, a biotechnology company partnering with the Moran Eye Center to commercialize scientific discoveries, where he serves as CSO and Board Member.

Research topics

• Medicine
• Biology
• Ophthalmology
• Genetics
• Bioinformatics
• Optometry
• Biochemistry
• Neuroscience
• Anatomy

Selected publications

• Retinopathy caused by a primary immune regulatory disorder - the spectrum of AIRE-associated retinopathy: case series and literature review

  Eye · 2026-04-09

  articleOpen access

  BACKGROUND/OBJECTIVE: Retinal involvement in autoimmune polyendocrine syndrome type 1 (APS1), a rare monogenic autoimmune disorder caused by mutations in the AIRE gene, is increasingly recognised but remains poorly defined. Prior reports suggest a variable phenotype, ranging from mild changes to severe vision loss, often presumed untreatable. We explored the range of retinal phenotypes associated with AIRE gene deficiency in a multicentre case series of patients with APS1. METHODS: We performed a retrospective case note review of patients with molecularly confirmed APS1 from tertiary ophthalmic centres. Clinical history, multimodal retinal imaging, electrophysiology, genetic data, and treatment regimens were analysed. Histopathology was available in one case postmortem. RESULTS: Records were reviewed from five unrelated female patients. Median age was 14 years at onset of ocular involvement and 33 years at most recent follow up. Some findings from two cases have been previously reported. Three distinct pathogenic AIRE variants contributing to biallelic genotypes were observed. Retinal findings ranged from structurally and functionally normal to advanced degeneration. One patient demonstrated sharp zonal atrophy on histopathology. Inflammatory features predominated in two cases, both showing durable vision preservation with periocular or systemic immunomodulation. One patient demonstrated four years of disease stabilisation with rituximab. No consistent genotype-phenotype correlation emerged. CONCLUSION: AIRE-associated retinopathy encompasses a diverse spectrum, from clinically silent to profound degeneration. Early, targeted immunomodulation might preserve vision in selected cases. These findings advocate for ophthalmic surveillance in APS1, and support further investigation into predictive biomarkers and possible tailored immunotherapy in this vision-threatening autoimmune disorder.

  PublisherOA PDFDOI

• Age-related macular degeneration and cerebral amyloid angiopathy have similar pathologies from cholesterol-APOE-amyloid-β-complement mediated inflammation

  Progress in Retinal and Eye Research · 2026-02-17

  articleOpen access
  PublisherOA PDFDOI

• Carotenoid Status and Psychological Impact of Presymptomatic Macular Degeneration Genetic Risk Assessment: The MAGENTA Randomized Trial

  Ophthalmology Science · 2026-01-23

  articleOpen access

  Purpose: Genetic testing for age-related macular degeneration (AMD) risk reliably offers insight into an individual's susceptibility for future visual loss; however, an American Academy of Ophthalmology expert panel in 2012 discouraged routine AMD genetic risk testing because there was no evidence that such knowledge would alter an individual's clinical course. To address this knowledge gap, we investigated whether disclosure of AMD genetic risk to presymptomatic individuals would encourage healthier lifestyle adoption that could reduce the incidence of AMD later in life. Design: The Moran AMD Genetic Testing Assessment (MAGENTA) trial is a single-site, prospective, controlled clinical study (NCT05265624) that randomized 80 presymptomatic subjects in a 3:1 ratio to immediate or 1-year deferred disclosure groups. We stratified participants into high-, intermediate-, and low-risk groups by Mendelian randomization. Subjects: We enrolled Whites aged 18 to 64 years with no clinical signs of AMD. Methods: As a biomarker of healthy nutritional status, participants' skin, plasma, and macular carotenoid concentrations were measured using resonance Raman and reflectance spectroscopies, high-performance liquid chromatography, and autofluorescence imaging, respectively. Nutritional and emotional status were assessed with validated surveys. Main Outcome Measures: We looked for changes in skin, plasma, and macular carotenoids as biomarkers of healthier lifestyle adoption and for the impact of AMD genetic risk disclosure on participants' psychological well-being. Results: > 0.05 for all comparisons). Participants' interest and compliance were high, as shown by the 95% subject study completion rate, and there was no evidence of worsening stress following AMD genetic risk disclosure to the participants. Conclusions: While AMD genetic risk disclosure did not significantly impact nutritional biomarker levels over 12 months, there were no adverse psychological effects, and the subjects generally felt knowledge of their AMD risk was valuable. Our findings could guide future presymptomatic AMD genetic testing trials with extended biomarker assessments in larger and more diverse populations. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

  PublisherOA PDFDOI

• Common Haplotypes within the Chromosome 1q31.3 Region Determine Systemic Concentrations of the Entire Complement Factor H Protein Family

  Journal of Innate Immunity · 2025-03-26 · 4 citations

  articleOpen access

  INTRODUCTION: The alternative pathway of complement activation is consistently active, keeping the complement system primed for immediate response. This constant "tick-over" mechanism is regulated by the factor H (FH) protein family, which encompasses seven highly related proteins: FH, FHL-1, and five FH-related (FHR-1 to -5) proteins. The current model is that the FHRs compete with FH and FHL-1 to fine-tune their activities. Genetic studies of this complex locus have revealed distinct haplotypes associating with a wide array of human diseases, underscoring its significant role in complement regulation. Nevertheless, a comprehensive analysis of systemic concentrations of all FH protein family members, accounting for known genetic variability within the population, is still lacking. METHODS: Systemic levels of each member of the FH protein family were quantified with the use of recently developed target specific ELISAs. Next, a genetic analysis focused on the chromosome 1q31.3 region was performed using next generation sequencing and multiplex ligase probe-dependent amplification. RESULTS: We report systemic protein levels of each member of the FH protein family found in vivo and demonstrate common haplotypes within the CFH locus give rise to classifiable protein expression patterns, establishing distinct ratios between FH, FHL-1, and the FHRs. CONCLUSIONS: The established reference intervals and identified genetic effects provide a benchmark for further research and emphasize the importance of including all family members when studying their role in both health and disease.

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• 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 access

  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

• Radiance Field Sampling for Unresolved Specular Object Classification

  2024-08-14

  article

  We introduce a novel technique for classifying unresolved specular objects. In remote sensing targets of interest like drones, helicopters, planes, cars, or satellites are often under-resolved. If those targets have specular surface characteristics, like metallic bodies or windows for example, there will be “glint” instances in detection which correspond to high signal levels from the specular surface on that target. The radiance field from a specular surface will be distributed spatially in a way that depends on the shape of that surface. And, as the target, source, or imaging system moves, one can collect a time-series sample of that radiance field and use that data to classify the unresolved surface which generated that field. This allows us to extract useful target information even if we are operating in an unresolved and/or turbulent regime, since specular signals provide high-signal information about the surface compared to diffuse surfaces, especially at long ranges. By employing both active and passive illumination schemes we demonstrate this concept in the lab and at a range of 4.7 km.

  PublisherDOI

• Levels of the HtrA1 Protein in Serum and Vitreous Humor Are Independent of Genetic Risk for Age-Related Macular Degeneration at the 10q26 Locus

  Investigative Ophthalmology & Visual Science · 2024-04-22 · 3 citations

  articleOpen accessSenior author

  Purpose: The purpose of this study was to determine if levels of the HtrA1 protein in serum or vitreous humor are influenced by genetic risk for age-related macular degeneration (AMD) at the 10q26 locus, age, sex, AMD status, and/or AMD disease severity, and, therefore, to determine the contribution of systemic and ocular HtrA1 to the AMD disease process. Methods: A custom-made sandwich ELISA assay (SCTM ELISA) for detection of the HtrA1 protein was designed and compared with three commercial assays (R&D Systems, MyBiosource 1 and MyBiosource 2) using 65 serum samples. Concentrations of HtrA1 were thereafter determined in serum and vitreous samples collected from 248 individuals and 145 human donor eyes, respectively. Results: The SCTM ELISA demonstrated high specificity, good recovery, and parallelism within its linear detection range and performed comparably to the R&D Systems assay. In contrast, we were unable to demonstrate the specificity of the two assays from MyBioSource using either recombinant or native HtrA1. Analyses of concentrations obtained using the validated SCTM assay revealed that genetic risk at the 10q26 locus, age, sex, or AMD status are not significantly associated with altered levels of the HtrA1 protein in serum or in vitreous humor (P > 0.05). Conclusions: HtrA1 levels in serum and vitreous do not reflect the risk for AMD associated with the 10q26 locus or disease status. Localized alteration in HTRA1 expression in the retinal pigment epithelium, rather than systemic changes in HtrA1, is the most likely driver of elevated risk for developing AMD among individuals with risk variants at the 10q26 locus.

  PublisherOA PDFDOI

• The vascular geometry of the choriocapillaris is associated with spatially heterogeneous molecular exchange with the outer retina

  The Journal of Physiology · 2024-03-21 · 2 citations

  articleOpen access

  Vision relies on the continuous exchange of material between the photoreceptors, retinal pigment epithelium and choriocapillaris, a dense microvascular bed located underneath the outer retina. The anatomy and physiology of the choriocapillaris and their association with retinal homeostasis have proven difficult to characterize, mainly because of the unusual geometry of this vascular bed. By analysing tissue dissected from 81 human eyes, we show that the thickness of the choriocapillaris does not vary significantly over large portions of the macula or with age. Assessments of spatial variations in the anatomy of the choriocapillaris in three additional human eyes indicate that the location of arteriolar and venular vessels connected to the plane of the choriocapillaris is non-random, and that venular insertions cluster around arteriolar ones. Mathematical models built upon these anatomical analyses reveal that the choriocapillaris contains regions where the transport of passive elements is dominated by diffusion, and that these diffusion-limited regions represent areas of reduced exchange with the outer retina. The width of diffusion-limited regions is determined by arterial flow rate and the relative arrangement of arteriolar and venular insertions. These analyses demonstrate that the apparent complexity of the choriocapillaris conceals a fine balance between several anatomical and functional parameters to effectively support homeostasis of the outer retina. KEY POINTS: The choriocapillaris is the capillary bed supporting the metabolism of photoreceptors and retinal pigment epithelium, two critical components of the visual system located in the outer part of the retina. The choriocapillaris has evolved a planar multipolar vascular geometry that differs markedly from the branched topology of most vasculatures in the human body. Here, we report that this planar multipolar vascular geometry is associated with spatially heterogenous molecular exchange between choriocapillaris and outer retina. Our data and analyses highlight a necessary balance between choriocapillaris anatomical and functional parameters to effectively support homeostasis of the outer retina.

  PublisherOA PDFDOI

• Author Response: Levels of the HtrA1 Protein in Serum and Vitreous Humor Are Independent of Genetic Risk for Age-Related Macular Degeneration at the 10q26 Locus

  Investigative Ophthalmology & Visual Science · 2024-12-12

  articleOpen accessSenior authorCorresponding

  recombinant HtrA1 in a linear manner in the SCTM ELISA.Despite this, there was no detectable signal when quantifying the MBS standards in the MBS diluents in the SCTM ELISA (see Supplementary Fig. S5).In conclusion, our article provides a robust validation of the SCTM ELISA and convincingly shows that neither the MBS1 assay nor the MBS2 assay is likely to detect native HtrA1.We invite Pan and Iwata 1 to reassess their original findings, 3 based on the MBS2 assay, using a validated and robust method to specifically and selectively quantify HtrA1 protein.Without this key validation step, a requisite for the scientific method, it is not possible to compare any HtrA1 ELISA with their results.

  PublisherOA PDFDOI

• Levels of complement factor H-related 4 protein do not influence susceptibility to age-related macular degeneration or its course of progression

  Nature Communications · 2024-01-10 · 12 citations

  articleOpen accessSenior author

  Dysregulation of the alternative pathway (AP) of the complement system is a significant contributor to age-related macular degeneration (AMD), a primary cause of irreversible vision loss worldwide. Here, we assess the contribution of the liver-produced complement factor H-related 4 protein (FHR-4) to AMD initiation and course of progression. We show that FHR-4 variation in plasma and at the primary location of AMD-associated pathology, the retinal pigment epithelium/Bruch's membrane/choroid interface, is entirely explained by three independent quantitative trait loci (QTL). Using two distinct cohorts composed of a combined 14,965 controls and 20,741 cases, we ascertain that independent QTLs for FHR-4 are distinct from variants causally associated with AMD, and that FHR-4 variation is not independently associated with disease. Additionally, FHR-4 does not appear to influence AMD progression course among patients with disease driven predominantly by AP dysregulation. Modulation of FHR-4 is therefore unlikely to be an effective therapeutic strategy for AMD.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01EY011515

  NIH · $4.2M · 2006

• NIH Grant R24EY017404

  NIH · $14.8M · 2012

• NIH Grant R01EY006463

  NIH · $3.2M · 2001

Frequent coauthors

• Lincoln V. Johnson

  Menlo School

  51 shared

• David J. Salant

  34 shared

• Karen M. Gehrs

  University of Iowa Hospitals and Clinics

  33 shared

• Reinhard WuCombining Diaeresisrzner

  Radboud University Nijmegen

  32 shared

• Don H. Anderson

  University of California, Santa Barbara

  32 shared

• Seppo Meri

  University of Helsinki

  31 shared

• Peter F. Zipfel

  27 shared

• H. Terence Cook

  Imperial College Healthcare NHS Trust

  26 shared

Education

• Ph.D., Biology and Marine Biology

  University of Southern California

• B.S., Biology and Marine Biology

  University of Southern California

Awards & honors

• Trustee Award from the Foundation Fighting Blindness
• Alcon Research Institute Award
• Fondazione G.B. Bietti Award
• Lew R. Wasserman Merit Award
• Olga Keith Wiess Scholar