Selective loss of S-cones in diabetic retinopathy

Arch Ophthalmol. 2000 Oct;118(10):1393-400. doi: 10.1001/archopht.118.10.1393.


Objective: To determine whether selective cone loss could explain the acquired tritan-like color confusion found in diabetic retinopathy.

Methods: Terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick end labeling (TUNEL) was employed on paraffin sections of retinas from 5 donors with diabetic retinopathy. For quantitative analysis, postmortem retinas were obtained from 13 human donors; 7 from patients with various durations and stages of diabetic retinopathy (4 background, 3 proliferative) and 6 controls. Enzyme histochemical analysis for carbonic anhydrase (CA) was used to distinguish L/M-cones (positive for CA) from S-cones (negative for CA). Cone topography was determined by sampling 360 degrees from 0.1 to 1.5 mm of foveal eccentricity and along the horizontal meridians from 1.5 to 15.0 mm.

Results: Rare cells in both the inner and outer nuclear layers of the diabetic eyes were positively labeled with the TUNEL method. The CA staining revealed incomplete and patchy losses of S-cones that were limited to the diabetic retinas. Statistically significant reduction in the density of S-cones was found at nearly all foveal eccentricities from 0.1 mm to 15.0 mm. This was not the case for the L/M-cones. On average, for all locations, the percentage of S-cones compared with L/M-cones was decreased by 21.0% +/- 3.4% with respect to the controls.

Conclusion: The S-cones selectively die in diabetic retinopathy.

Clinical relevance: Selective loss of S-cones may contribute to the tritan-like color vision deficit seen in patients with diabetic retinopathy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Carbonic Anhydrases / analysis
  • Cell Count
  • Cell Death
  • Child
  • Color Vision Defects / diagnosis*
  • Color Vision Defects / enzymology
  • Diabetic Retinopathy / diagnosis*
  • Diabetic Retinopathy / enzymology
  • Female
  • Histocytochemistry
  • Humans
  • In Situ Nick-End Labeling
  • Male
  • Middle Aged
  • Retinal Cone Photoreceptor Cells / enzymology
  • Retinal Cone Photoreceptor Cells / pathology*
  • Visual Acuity


  • Carbonic Anhydrases