About

Rando L. Allikmets, PhD, is the William and Donna Acquavella Professor of Ophthalmic Sciences at Columbia University Irving Medical Center, with appointments in Ophthalmology and Pathology and Cell Biology. His research focuses on using the human genome sequence to assess genetic variation in the population, aiming to answer questions about genetic predispositions to inherited and complex disorders, particularly eye diseases. His laboratory specializes in discovering genetic defects underlying these disorders, cloning and characterizing relevant genes, and determining mutation spectra associated with specific phenotypes. A significant part of his work involves systematic screening of candidate genes, especially those in the ATP-binding cassette (ABC) transporter superfamily, which are vital membrane proteins involved in cellular transport functions. His contributions have advanced understanding of the molecular genetic basis of retinal diseases such as Stargardt macular dystrophy, cone-rod dystrophy, retinitis pigmentosa, and age-related macular degeneration.

Research topics

• Biology
• Genetics
• Computational biology
• Medicine
• Biochemistry
• Pathology
• Internal medicine

Selected publications

• Precision Diagnosis in <i>APOL1</i> Kidney Disease With the p.N264K M1 Protective Variant

  JAMA Network Open · 2026-03-11

  articleOpen access

  Importance: The APOL1 M1 (p.N264K) variant protects against G2-associated APOL1 focal segmental glomerulosclerosis (FSGS) and chronic kidney disease (CKD). However, the utility of knowing an individual's M1 status in guiding kidney disease diagnosis and other clinical scenarios remains underexplored. Objective: To test 2 hypotheses: (1) in patients with APOL1 high-risk (HR) genotype kidney disease with at least 1 G2 allele, M1 can distinguish APOL1 CKD from non-APOL1 CKD; (2) in people with APOL1 low-risk (LR) genotypes, M1 is independently associated with protection against FSGS and CKD. Design, Setting, and Participants: Retrospective case-control study using data from 2 tertiary care hospitals (Columbia University Irving Medical Center and Mass General Brigham Biobank) and population-based data (the UK Biobank [UKB], Electronic Medical Records and Genomics [eMERGE-III], and All of Us [AoU]). Participants were individuals with a diagnosis of FSGS or steroid-resistant nephrotic syndrome (SRNS), individuals with CKD, and controls. Exposures: Exposures included the M1 variant (p.N264K) obtained from exome or genome sequencing data, sex, and genetic ancestry. Main outcome and measure: The main outcome was the presence or absence of kidney disease, defined as FSGS or non-FSGS CKD, compared with non-kidney disease controls. Association between the M1 variant and disease status was assessed using odds ratios (ORs). Results: A total of 107 696 individuals (54 994 [51.1%] female; 8779 [8.2%] with African ancestry, 78 475 [72.9%] with European ancestry, and 16 129 [15.0%] with multiethnic ancestry), including 3460 with FSGS or SRNS, 24 382 with non-FSGS CKD kidney disease, and 79 854 controls were enrolled in the discovery cohort. In the APOL1-HR group (1413 participants), M1 was significantly inversely associated with FSGS or SRNS cases compared with controls without kidney disease (OR, 0.20; 95% CI, 0.04-0.63; P = 3.69 × 10-3). Among individuals with CKD with APOL1-HR genotypes, M1 was 4 times more frequent in those whose CKD was not due to FSGS or SRNS. Importantly, electronic health record and biopsy review identified an alternative, non-APOL1 cause for CKD in nearly all APOL1-HR-M1 cases. There was no association between individuals with APOL1-LR genotypes with M1 and protection against CKD or FSGS. Conclusions and relevance: In this case-control study of 107 696 individuals, presence of an APOL1-HR genotype M1 was significantly associated with protection against kidney disease, suggesting that it may have a role as a genetic modifier. Patients with CKD with an APOL1-HR genotype and M1 should be evaluated for an alternative and potentially treatable cause of their CKD.

  PublisherOA PDFDOI

• Characterization of the Subclinical Perilesional Zone in the Macula of Early-Stage ABCA4 Disease

  Translational Vision Science & Technology · 2025-12-23

  articleOpen accessSenior authorCorresponding

  Purpose: To characterize photoreceptor layer thinning in clinically unremarkable regions adjacent to the atrophic lesion in early-stage ABCA4 disease eyes. Methods: Twenty-seven patients with confined atrophic lesions (≤3.5 mm in diameter) were included. Two pathogenic alleles were confirmed by sequencing of the ABCA4 locus. Multimodal imaging included fundus photography, short-wavelength autofluorescence, and near-infrared autofluorescence imaging (NIR-AF). Total receptor+ (TREC+) thickness was segmented in spectral-domain optical coherence tomography (SD-OCT) scans in patient eyes (n = 27) along with age-matched healthy control eyes (n = 20). Results: Mean age of the study cohort was 24.1 years, and 15 of 27 (55.6%) patients harbored genotypes consisting of the p.(Gly1961Glu) variant of the ABCA4 gene. Atrophic lesions ranged from 0.61 to 3.13 mm in diameter (μ = 1.73, σ = 0.70). Six patients had mild RPE mottling adjacent to the lesion on NIR-AF. The atrophic lesion corresponded to a disruption of photoreceptor-attributable bands on SD-OCT, while all layers were visibly intact outside the lesion. TREC+ thickness in patient eyes was <0.15 mm (below 4σ) of healthy control thickness immediately adjacent to the lesion edge and gradually normalized to within ±2σ at ≈1.2 mm eccentricity from the fovea. Conclusions: A uniform subclinical perilesional zone of photoreceptor thinning extends around the perimeter of early-stage atrophic lesions in ABCA4 disease. This region spatially maps to known regions of vision loss and more accurately approximates the extent of photoreceptor abnormality compared to disease changes visible on standard fundus imaging. Translational Relevance: Semi-automated segmentation of SD-OCT scans identifies a consistent subclinical biomarker relevant to early photoreceptor degeneration in ABCA4 disease.

  PublisherOA PDFDOI

• Towards Uncovering the Role of Incomplete Penetrance in Maculopathies through Sequencing of 105 Disease-Associated Genes

  Biomolecules · 2024-03-19 · 7 citations

  articleOpen access

  Inherited macular dystrophies (iMDs) are a group of genetic disorders, which affect the central region of the retina. To investigate the genetic basis of iMDs, we used single-molecule Molecular Inversion Probes to sequence 105 maculopathy-associated genes in 1352 patients diagnosed with iMDs. Within this cohort, 39.8% of patients were considered genetically explained by 460 different variants in 49 distinct genes of which 73 were novel variants, with some affecting splicing. The top five most frequent causative genes were ABCA4 (37.2%), PRPH2 (6.7%), CDHR1 (6.1%), PROM1 (4.3%) and RP1L1 (3.1%). Interestingly, variants with incomplete penetrance were revealed in almost one-third of patients considered solved (28.1%), and therefore, a proportion of patients may not be explained solely by the variants reported. This includes eight previously reported variants with incomplete penetrance in addition to CDHR1:c.783G&gt;A and CNGB3:c.1208G&gt;A. Notably, segregation analysis was not routinely performed for variant phasing—a limitation, which may also impact the overall diagnostic yield. The relatively high proportion of probands without any putative causal variant (60.2%) highlights the need to explore variants with incomplete penetrance, the potential modifiers of disease and the genetic overlap between iMDs and age-related macular degeneration. Our results provide valuable insights into the genetic landscape of iMDs and warrant future exploration to determine the involvement of other maculopathy genes.

  PublisherOA PDFDOI

• Cross-Sectional Analysis of Outer Retinal Tubulation in Inherited Retinal Diseases: A Multicenter Study

  American Journal of Ophthalmology · 2024-08-09 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• Serine and glycine physiology reversibly modulate retinal and peripheral nerve function

  Cell Metabolism · 2024-08-26 · 18 citations

  article
  PublisherDOI

• Characterization of the Subclinical Perilesional Zone in the Macula of Early-Stage ABCA4 Disease

  medRxiv · 2024-11-18 · 1 citations

  preprintOpen accessCorresponding

  A bstract Purpose To characterize photoreceptor layer thinning in clinically unremarkable regions adjacent to the atrophic lesion in early-stage ABCA4 disease eyes. Methods 27 patients with confined atrophic lesions ( ≤ 3.5mm in diameter) were included. Two pathogenic alleles were confirmed by sequencing of the ABCA4 locus. Multimodal imaging included color fundus photography, short wavelength-autofluorescence (SW-AF) and near infrared-autofluorescence (NIR-AF) imaging. Total receptor+ (TREC+) thickness was segmented in spectral domain-optical coherence tomography (SD-OCT) scans in patient eyes (n=27) along with age-matched healthy control eyes (n=20). Results µ age of the study cohort was 24.1 years and 15/27 (55.6%) patients harbored genotypes consisting of the p.(Gly1961Glu) variant in ABCA4 . Atrophic lesions in the central macula ranged from 0.61 to 3.13 mm in diameter ( µ = 1.73, σ = 0.70). Six patients had mild RPE mottling adjacent to the lesion on NIR-AF. The atrophic lesion corresponded to a disruption of photoreceptor-attributable bands on SD-OCT while all layers were visibly intact outside the lesion. TREC+ thickness in patient eyes were &lt;0.15 mm or below 4 σ of normal control eyes immediately adjacent to the lesion edge and gradually normalized to within ± 2 σ at ≈ 1.2 mm eccentricity from the fovea. Conclusion A uniform subclinical perilesional zone (SPZ) of photoreceptor thinning extends around the perimeter of early-stage atrophic lesions in ABCA4 disease. This region spatially maps to known regions of vision loss and more accurately approximates the extent of photoreceptor abnormality compared to the disease changes visible on standard fundus imaging. Translational relevance Semi-automated segmentation of SD-OCT scans identifies a consistent subclinical biomarker relevant to early photoreceptor degeneration in ABCA4 disease.

  PublisherOA PDFDOI

• Targeted sequencing and in vitro splice assays shed light on ABCA4-associated retinopathies missing heritability

  Human Genetics and Genomics Advances · 2023-09-12 · 12 citations

  articleOpen access

  The ABCA4 gene is the most frequently mutated Mendelian retinopathy-associated gene. Biallelic variants lead to a variety of phenotypes, however, for thousands of cases the underlying variants remain unknown. Here, we aim to shed further light on the missing heritability of ABCA4-associated retinopathy by analyzing a large cohort of macular dystrophy probands. A total of 858 probands were collected from 26 centers, of whom 722 carried no or one pathogenic ABCA4 variant, while 136 cases carried two ABCA4 alleles, one of which was a frequent mild variant, suggesting that deep-intronic variants (DIVs) or other cis-modifiers might have been missed. After single molecule molecular inversion probes (smMIPs)-based sequencing of the complete 128-kb ABCA4 locus, the effect of putative splice variants was assessed in vitro by midigene splice assays in HEK293T cells. The breakpoints of copy number variants (CNVs) were determined by junction PCR and Sanger sequencing. ABCA4 sequence analysis solved 207 of 520 (39.8%) naive or unsolved cases and 70 of 202 (34.7%) monoallelic cases, while additional causal variants were identified in 54 of 136 (39.7%) probands carrying two variants. Seven novel DIVs and six novel non-canonical splice site variants were detected in a total of 35 alleles and characterized, including the c.6283-321C>G variant leading to a complex splicing defect. Additionally, four novel CNVs were identified and characterized in five alleles. These results confirm that smMIPs-based sequencing of the complete ABCA4 gene provides a cost-effective method to genetically solve retinopathy cases and that several rare structural and splice altering defects remain undiscovered in Stargardt disease cases.

  PublisherDOI

• Insights Into <i>PROM1</i>-Macular Disease Using Multimodal Imaging

  Investigative Ophthalmology & Visual Science · 2023-04-24 · 8 citations

  articleOpen access

  Purpose: To describe the features of genetically confirmed PROM1-macular dystrophy in multimodal images. Methods: Thirty-six (36) eyes of 18 patients (5-66 years; mean age, 42.4 years) were prospectively studied by clinical examination and multimodal imaging. Short-wavelength autofluorescence (SW-AF) and quantitative fundus autofluorescence (qAF) images were acquired with a scanning laser ophthalmoscope (HRA+OCT, Heidelberg Engineering) modified by insertion of an internal autofluorescent reference. Further clinical testing included near-infrared autofluorescence (NIR-AF; HRA2, Heidelberg Engineering) with semiquantitative analysis, spectral domain-optical coherence tomography (HRA+OCT) and full-field electroretinography. All patients were genetically confirmed by exome sequencing. Results: All 18 patients presented with varying degrees of maculopathy. One family with individuals affected across two generations exhibited granular fleck-like deposits across the posterior pole. Areas of granular deposition in SW-AF and NIR-AF corresponded to intermittent loss of the ellipsoid zone, whereas discrete regions of hypoautofluorescence corresponded with a loss of outer retinal layers in spectral-domain optical coherence tomography scans. For 18 of the 20 eyes, qAF levels within the macula were within the 95% confidence intervals of healthy age-matched individuals; nor was the mean NIR-AF signal increased relative to healthy eyes. Conclusions: Although PROM1-macular dystrophy (Stargardt disease 4) can exhibit phenotypic overlap with recessive Stargardt disease, significantly increased SW-AF levels were not detected. As such, elevated bisretinoid lipofuscin may not be a feature of the pathophysiology of PROM1 disease. The qAF approach could serve as a method of early differential diagnosis and may help to identify appropriate disease targets as therapeutics become available to treat inherited retinal disease.

  PublisherDOI

• Monitoring Lesion Area Progression in Stargardt Disease: A Comparison of En Face Optical Coherence Tomography and Fundus Autofluorescence

  Translational Vision Science & Technology · 2023-05-01 · 6 citations

  articleOpen access

  Purpose: To compare longitudinal changes in en face spectral domain-optical coherence tomography (SD-OCT) measurements of ellipsoid zone (EZ) and retinal pigment epithelium (RPE) loss to changes in the hypoautofluorescent and hyperautofluorescent (AF) areas detected with short-wavelength (SW)-AF in ABCA4-associated retinopathy. Methods: SD-OCT volume scans were obtained from 20 patients (20 eyes) over 2.6 ± 1.2 years (range 1-5 years). The EZ, and RPE/Bruch's membrane boundaries were segmented, and en face slab images generated. SubRPE and EZ slab images were used to measure areas of atrophic RPE and EZ loss. These were compared to longitudinal measurements of the hypo- and abnormal AF (hypoAF and surrounding hyperAF) areas. Results: At baseline, the en face area of EZ loss was significantly larger than the subRPE atrophic area, and the abnormal AF area was significantly larger than the hypoAF area. The median rate of EZ loss was significantly greater than the rate of increase in the subRPE atrophic area (1.2 mm2/yr compared to 0.5 mm2/yr). The median rate of increase in the abnormal AF area was significantly greater than the increase in the hypoAF area (1.6 mm2/yr compared to 0.6 mm2/yr). Conclusions: En face SD-OCT can be used to quantify changes in RPE atrophy and photoreceptor integrity. It can be a complementary or alternative technique to SW-AF with the advantage of monitoring EZ loss. The SW-AF results emphasize the importance of measuring changes in the hypo- and abnormal AF areas. Translational Relevance: The findings are relevant to the selection of outcome measures for monitoring ABCA4-associated retinopathy.

  PublisherOA PDFDOI

• Re: Agrón et al.: Reticular pseudodrusen status, ARMS2/HTRA1 genotype, and geographic atrophy enlargement: Age-Related Eye Disease Study 2 Report 32. (Ophthalmology. 2022;129:1107–1119)

  Ophthalmology · 2023-04-27

  letterOpen access
  PublisherOA PDFDOI

Recent grants

• Core Facilities for Vision Research

  NIH · $12.4M · 2010–2026

• NIH Grant R24EY019861

  NIH · $5.7M · 2017

• Integrated clinical, genetic and functional analysis of the ABCA4 locus

  NIH · $2.2M · 2019–2025

• NIH Grant R01EY013435

  NIH · $7.7M · 2016

• Precision medicine for ABCA4 disease: modifier alleles

  NIH · $2.3M · 2018–2023

Frequent coauthors

• Michael Dean

  Division of Cancer Epidemiology and Genetics

  210 shared

• Eugene R. Zabarovsky

  162 shared

• В. И. Кашуба

  National Academy of Sciences of Ukraine

  160 shared

• Lev L. Kisselev

  156 shared

• George Klein

  153 shared

• V Bannikov

  146 shared

• Gösta Winberg

  Ludwig Cancer Research

  133 shared

• Rinat Gizatullin

  Karolinska Institutet

  133 shared

Awards & honors

• 2012 Dario Lorenzetti Lecture, McGill University, Montreal,…
• 2010 Foundation Fighting Blindness Visionary Award
• 2008 Mette Warburg Lecture, the Kennedy Center, University o…
• 2007 Alcon Research Institute Award
• 2006 Awarded the title of “Godfather”, Association DMLA (AMD…