June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Retinal Pericyte Density Declines Before the Onset of Clinically-apparent Diabetic Retinopathy while Increased Non-perfusion Drives Leakage
Author Affiliations & Notes
  • Bonnie Bertha Huang
    Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Hisashi Fukuyama
    Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Nicholas Konopek
    Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Stephen A. Burns
    School of Optometry, Indiana University, Bloomington, Indiana, United States
  • Amani A Fawzi
    Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Footnotes
    Commercial Relationships   Bonnie Huang None; Hisashi Fukuyama None; Nicholas Konopek None; Stephen Burns None; Amani Fawzi Regeneron, Roche/Genentech, Boehringer Ingelheim, RegenXbio, 3Helix, Code C (Consultant/Contractor), Boehringer Ingelheim, Code F (Financial Support)
  • Footnotes
    Support  NIH Grant R01EY31815, NIH Grant 1T35DK126628-01, Grant from the Illinois Society for the Prevention of Blindness
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3839. doi:
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      Bonnie Bertha Huang, Hisashi Fukuyama, Nicholas Konopek, Stephen A. Burns, Amani A Fawzi; Retinal Pericyte Density Declines Before the Onset of Clinically-apparent Diabetic Retinopathy while Increased Non-perfusion Drives Leakage. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3839.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Pericyte loss has been posited to be the crucial initial event in the pathologic cascade of diabetic retinopathy (DR), but this has not been verified in living humans. Here, we used adaptive optics scanning laser ophthalmology (AOSLO) to quantify pericyte density in healthy subjects and those with diabetes but no apparent DR (DMnoDR). We also analyzed pericyte density and optical coherence tomography angiography (OCTA) in eyes with diabetic macular edema (DME).

Methods : We examined 17 healthy controls, 15 DMnoDR subjects, and 3 patients with DME and mild-moderate nonproliferative DR. For each vessel of interest, we imaged the vascular wall using AOSLO. For each vessel location, pericyte density was quantified as the number of pericytes/100 µm. OCTA vessel density (VD) values were obtained from the built-in AngioVue Analytics software. Student’s t-test was performed for statistical analysis.

Results : DMnoDR eyes had a lower pericyte density than healthy eyes (5.0 ± 2.1 versus 6.5 ± 2.0 pericytes per 100 µm, p = 0.044). Although DME eyes did not have a statistically significantly lower pericyte density than DMnoDR eyes (p = 0.72), they had significantly lower VD in the superficial and deep capillary plexuses (p = 0.002, 0.0003 respectively).

Conclusions : Our results indicate that pericyte density can serve as a quantitative biomarker of preclinical DR since it declines well before the onset of clinical DR. This could help guide the optimal timing of therapeutics aimed at preserving pericytes to prevent DR. We were surprised to find that eyes with DME did not show significantly lower pericyte density than eyes with DMnoDR. However, interestingly DME eyes did have significantly decreased VD suggesting that leakage is driven not only by pericyte loss but also by a higher load of retinal nonperfusion and ischemia, indicators of higher VEGF load.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

a) Example vessel with a high pericyte density from a healthy subject. b) Example vessel with a low pericyte density from a DMnoDR patient. c) Each dot represents the average of all pericyte densities (reported as number of pericytes per 100 µm) for all measured vessel locations in each subject. P = 0.044

a) Example vessel with a high pericyte density from a healthy subject. b) Example vessel with a low pericyte density from a DMnoDR patient. c) Each dot represents the average of all pericyte densities (reported as number of pericytes per 100 µm) for all measured vessel locations in each subject. P = 0.044

 

a) Example OCTA scan of a DMnoDR eye with a high VD. b) Example OCTA scan of a DME eye with a low VD. c) Each dot represents the VD for one eye. P = 0.002

a) Example OCTA scan of a DMnoDR eye with a high VD. b) Example OCTA scan of a DME eye with a low VD. c) Each dot represents the VD for one eye. P = 0.002

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