Dose-dependent reduction of retinal vessel changes associated with diabetic retinopathy in galactose-fed dogs by the aldose reductase inhibitor M79175

Heike Neuenschwander, Yukio Takahashi, Peter F. Kador

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The onset and progression of retinal vascular changes associated with early diabetic retinopathy has been delayed in beagles fed 30% galactose diet for 38 months by treatment with the aldose reductase inhibitor M79175 (2- methyl-6-fluoro-spirochroman-4-5'-imidazolidine-2',4'-dione). Forty 9-month old male beagles were fed a dally diet containing either 30% non-nutrient filler or 30% galactose. One group of galactose-fed dogs was untreated while the others received M79175 at an average group dose of either 10 or 16 mg/kg/day. After 38 months one eye from 4 dogs from each group was enucleated and the isolated retinal vasculatures were objectively evaluated using an Olympus Cue-3 color image analysis system. Measurements of endothelium/pericyte (E/P) ratios, pericyte ghosts/1000 cells, pericytes and endothelial densities, and % acellularity per area and % acellularity per capillary length were conducted on a 0.1 mm square area surrounding the midpoints of 12 previously defined subregions. With the exception of endothelial densities which were not changed in galactose-fed dogs, M79175 treatment resulted in smaller changes in all parameters examined with the E/P ratio in dogs treated with 16 mg/kg/day M79175 not significantly different from that of age-matched non-galactose-fed dogs. These studies indicate that aldose reductase inhibitors provide dose-dependent protection against pericyte degeneration and subsequent microaneurysms formation.

Original languageEnglish (US)
Pages (from-to)517-528
Number of pages12
JournalJournal of Ocular Pharmacology and Therapeutics
Volume13
Issue number6
DOIs
StatePublished - Dec 1997

Fingerprint

Aldehyde Reductase
Retinal Vessels
Pericytes
Diabetic Retinopathy
Galactose
Dogs
Endothelium
Diet
Cues
Endothelial Cells
Color
M 79175

ASJC Scopus subject areas

  • Ophthalmology
  • Pharmacology
  • Pharmacology (medical)

Cite this

@article{f197faefce1e4d85b288f88237b3475e,
title = "Dose-dependent reduction of retinal vessel changes associated with diabetic retinopathy in galactose-fed dogs by the aldose reductase inhibitor M79175",
abstract = "The onset and progression of retinal vascular changes associated with early diabetic retinopathy has been delayed in beagles fed 30{\%} galactose diet for 38 months by treatment with the aldose reductase inhibitor M79175 (2- methyl-6-fluoro-spirochroman-4-5'-imidazolidine-2',4'-dione). Forty 9-month old male beagles were fed a dally diet containing either 30{\%} non-nutrient filler or 30{\%} galactose. One group of galactose-fed dogs was untreated while the others received M79175 at an average group dose of either 10 or 16 mg/kg/day. After 38 months one eye from 4 dogs from each group was enucleated and the isolated retinal vasculatures were objectively evaluated using an Olympus Cue-3 color image analysis system. Measurements of endothelium/pericyte (E/P) ratios, pericyte ghosts/1000 cells, pericytes and endothelial densities, and {\%} acellularity per area and {\%} acellularity per capillary length were conducted on a 0.1 mm square area surrounding the midpoints of 12 previously defined subregions. With the exception of endothelial densities which were not changed in galactose-fed dogs, M79175 treatment resulted in smaller changes in all parameters examined with the E/P ratio in dogs treated with 16 mg/kg/day M79175 not significantly different from that of age-matched non-galactose-fed dogs. These studies indicate that aldose reductase inhibitors provide dose-dependent protection against pericyte degeneration and subsequent microaneurysms formation.",
author = "Heike Neuenschwander and Yukio Takahashi and Kador, {Peter F.}",
year = "1997",
month = "12",
doi = "10.1089/jop.1997.13.517",
language = "English (US)",
volume = "13",
pages = "517--528",
journal = "Journal of Ocular Pharmacology and Therapeutics",
issn = "1080-7683",
publisher = "Mary Ann Liebert Inc.",
number = "6",

}

TY - JOUR

T1 - Dose-dependent reduction of retinal vessel changes associated with diabetic retinopathy in galactose-fed dogs by the aldose reductase inhibitor M79175

AU - Neuenschwander, Heike

AU - Takahashi, Yukio

AU - Kador, Peter F.

PY - 1997/12

Y1 - 1997/12

N2 - The onset and progression of retinal vascular changes associated with early diabetic retinopathy has been delayed in beagles fed 30% galactose diet for 38 months by treatment with the aldose reductase inhibitor M79175 (2- methyl-6-fluoro-spirochroman-4-5'-imidazolidine-2',4'-dione). Forty 9-month old male beagles were fed a dally diet containing either 30% non-nutrient filler or 30% galactose. One group of galactose-fed dogs was untreated while the others received M79175 at an average group dose of either 10 or 16 mg/kg/day. After 38 months one eye from 4 dogs from each group was enucleated and the isolated retinal vasculatures were objectively evaluated using an Olympus Cue-3 color image analysis system. Measurements of endothelium/pericyte (E/P) ratios, pericyte ghosts/1000 cells, pericytes and endothelial densities, and % acellularity per area and % acellularity per capillary length were conducted on a 0.1 mm square area surrounding the midpoints of 12 previously defined subregions. With the exception of endothelial densities which were not changed in galactose-fed dogs, M79175 treatment resulted in smaller changes in all parameters examined with the E/P ratio in dogs treated with 16 mg/kg/day M79175 not significantly different from that of age-matched non-galactose-fed dogs. These studies indicate that aldose reductase inhibitors provide dose-dependent protection against pericyte degeneration and subsequent microaneurysms formation.

AB - The onset and progression of retinal vascular changes associated with early diabetic retinopathy has been delayed in beagles fed 30% galactose diet for 38 months by treatment with the aldose reductase inhibitor M79175 (2- methyl-6-fluoro-spirochroman-4-5'-imidazolidine-2',4'-dione). Forty 9-month old male beagles were fed a dally diet containing either 30% non-nutrient filler or 30% galactose. One group of galactose-fed dogs was untreated while the others received M79175 at an average group dose of either 10 or 16 mg/kg/day. After 38 months one eye from 4 dogs from each group was enucleated and the isolated retinal vasculatures were objectively evaluated using an Olympus Cue-3 color image analysis system. Measurements of endothelium/pericyte (E/P) ratios, pericyte ghosts/1000 cells, pericytes and endothelial densities, and % acellularity per area and % acellularity per capillary length were conducted on a 0.1 mm square area surrounding the midpoints of 12 previously defined subregions. With the exception of endothelial densities which were not changed in galactose-fed dogs, M79175 treatment resulted in smaller changes in all parameters examined with the E/P ratio in dogs treated with 16 mg/kg/day M79175 not significantly different from that of age-matched non-galactose-fed dogs. These studies indicate that aldose reductase inhibitors provide dose-dependent protection against pericyte degeneration and subsequent microaneurysms formation.

UR - http://www.scopus.com/inward/record.url?scp=0031440825&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031440825&partnerID=8YFLogxK

U2 - 10.1089/jop.1997.13.517

DO - 10.1089/jop.1997.13.517

M3 - Article

C2 - 9436155

AN - SCOPUS:0031440825

VL - 13

SP - 517

EP - 528

JO - Journal of Ocular Pharmacology and Therapeutics

JF - Journal of Ocular Pharmacology and Therapeutics

SN - 1080-7683

IS - 6

ER -