Changes in Corneal Innervation and Sensitivity and Acetylcholine-mediated Vascular Relaxation of the Posterior Ciliary Artery in a Type 2 Diabetic Rat

Overview

Journal Invest Ophthalmol Vis Sci

Specialty Ophthalmology

Date 2012 Jan 26

PMID 22273725

Citations 37

Authors

Eric P Davidson

Lawrence J Coppey

Amey Holmes

Mark A Yorek

Affiliations

Soon will be listed here.

Abstract

Purpose: Corneal confocal microscopy is emerging as a clinical tool to evaluate the development and progression of diabetic neuropathy. The purpose of these studies was to characterize the changes in corneal sensitivity and innervation in a rat model of type 2 diabetes in relation to standard peripheral neuropathy endpoints. Assessment of diabetes-induced changes in corneal innervation and sensitivity in animal models will be important for determining the usefulness of corneal markers for preclinical studies to test potential new treatments for diabetic neuropathy.

Methods: High-fat/low-dose streptozotocin diabetic rats were used to examine diabetes-induced changes in standard diabetic neuropathy endpoints and innervation of the cornea using confocal microscopy, corneal sensitivity using a Cochet-Bonnet esthesiometer, and vascular reactivity of the posterior ciliary artery.

Results: Compared with age-matched control rats, the induction of hyperglycemia in rats fed high-fat diets caused a decrease in nerve conduction velocity, thermal hypoalgesia, and intraepidermal nerve fiber profiles. In the cornea there was a decrease in corneal nerve fiber length and sensitivity. In addition, vascular relaxation in response to acetylcholine was decreased in the posterior ciliary artery.

Conclusions: These studies suggest that in a type 2 diabetic rat model, changes in corneal nerve innervation and sensitivity occur that are consistent with changes seen in diabetic patients. Corneal sensitivity and innervation may be valuable endpoints for examining the potential treatments of diabetic neuropathy in preclinical studies.

Citing Articles

Combination therapy is it in the future for successfully treating peripheral diabetic neuropathy?.

Yorek M Front Endocrinol (Lausanne). 2024; 15:1357859.

PMID: 38812811 PMC: 11133577. DOI: 10.3389/fendo.2024.1357859.

In vivo corneal confocal microscopy as a non-invasive test to assess obesity induced small fibre nerve damage and inflammation.

Gulkas S, Aydin F, Akkaya Turhan S, Toker A Eye (Lond). 2022; 37(11):2226-2232.

PMID: 36443498 PMC: 10366092. DOI: 10.1038/s41433-022-02321-x.

Using Corneal Confocal Microscopy to Identify Therapeutic Agents for Diabetic Neuropathy.

Jolivalt C, Han M, Nguyen A, Desmond F, Jesus C, Vasconselos D J Clin Med. 2022; 11(9).

PMID: 35566433 PMC: 9104226. DOI: 10.3390/jcm11092307.

Peripheral Neuropathy Phenotyping in Rat Models of Type 2 Diabetes Mellitus: Evaluating Uptake of the Neurodiab Guidelines and Identifying Future Directions.

Hossain M, Kendig M, Letton M, Morris M, Arnold R Diabetes Metab J. 2022; 46(2):198-221.

PMID: 35385634 PMC: 8987683. DOI: 10.4093/dmj.2021.0347.

Lost in Translation? Measuring Diabetic Neuropathy in Humans and Animals.

Jin H, Moon S, Calcutt N Diabetes Metab J. 2020; 45(1):27-42.

PMID: 33307618 PMC: 7850880. DOI: 10.4093/dmj.2020.0216.

References

Gabbay K . Aldose reductase inhibition in the treatment of diabetic neuropathy: where are we in 2004?. Curr Diab Rep. 2004; 4(6):405-8. DOI: 10.1007/s11892-004-0047-z. View

Malik R, Kallinikos P, Abbott C, van Schie C, Morgan P, Efron N . Corneal confocal microscopy: a non-invasive surrogate of nerve fibre damage and repair in diabetic patients. Diabetologia. 2003; 46(5):683-8. DOI: 10.1007/s00125-003-1086-8. View

Calcutt N . Future treatments for diabetic neuropathy: clues from experimental neuropathy. Curr Diab Rep. 2003; 2(6):482-8. DOI: 10.1007/s11892-002-0117-z. View

Yin J, Huang J, Chen C, Gao N, Wang F, Yu F . Corneal complications in streptozocin-induced type I diabetic rats. Invest Ophthalmol Vis Sci. 2011; 52(9):6589-96. PMC: 3176029. DOI: 10.1167/iovs.11-7709. View

Tavakoli M, Quattrini C, Abbott C, Kallinikos P, Marshall A, Finnigan J . Corneal confocal microscopy: a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy. Diabetes Care. 2010; 33(8):1792-7. PMC: 2909064. DOI: 10.2337/dc10-0253. View

Tesfaye S, Selvarajah D . The Eurodiab study: what has this taught us about diabetic peripheral neuropathy?. Curr Diab Rep. 2009; 9(6):432-4. DOI: 10.1007/s11892-009-0070-1. View

Oltman C, Davidson E, Coppey L, Kleinschmidt T, Yorek M . Treatment of Zucker diabetic fatty rats with AVE7688 improves vascular and neural dysfunction. Diabetes Obes Metab. 2008; 11(3):223-33. PMC: 2667677. DOI: 10.1111/j.1463-1326.2008.00924.x. View

Obrosova I, Li F, Abatan O, Forsell M, Komjati K, Pacher P . Role of poly(ADP-ribose) polymerase activation in diabetic neuropathy. Diabetes. 2004; 53(3):711-20. DOI: 10.2337/diabetes.53.3.711. View

Pritchard N, Edwards K, Vagenas D, Shahidi A, Sampson G, Russell A . Corneal sensitivity as an ophthalmic marker of diabetic neuropathy. Optom Vis Sci. 2010; 87(12):1003-8. DOI: 10.1097/OPX.0b013e3181fd6188. View

10.

Tavakoli M, Hossain P, Malik R . Clinical applications of corneal confocal microscopy. Clin Ophthalmol. 2009; 2(2):435-45. PMC: 2693976. DOI: 10.2147/opth.s1490. View

11.

Mojaddidi M, Quattrini C, Tavakoli M, Malik R . Recent developments in the assessment of efficacy in clinical trials of diabetic neuropathy. Curr Diab Rep. 2005; 5(6):417-22. DOI: 10.1007/s11892-005-0048-6. View

12.

Oltman C, Davidson E, Coppey L, Kleinschmidt T, Dake B, Yorek M . Role of the effect of inhibition of neutral endopeptidase on vascular and neural complications in streptozotocin-induced diabetic rats. Eur J Pharmacol. 2010; 650(2-3):556-62. PMC: 3016620. DOI: 10.1016/j.ejphar.2010.10.047. View

13.

Pritchard N, Edwards K, Shahidi A, Sampson G, Russell A, Malik R . Corneal markers of diabetic neuropathy. Ocul Surf. 2011; 9(1):17-28. DOI: 10.1016/s1542-0124(11)70006-4. View

14.

Terata K, Coppey L, Davidson E, Dunlap J, Gutterman D, Yorek M . Acetylcholine-induced arteriolar dilation is reduced in streptozotocin-induced diabetic rats with motor nerve dysfunction. Br J Pharmacol. 1999; 128(3):837-43. PMC: 1571695. DOI: 10.1038/sj.bjp.0702856. View

15.

Oltman C, Davidson E, Coppey L, Kleinschmidt T, Lund D, Yorek M . Attenuation of vascular/neural dysfunction in Zucker rats treated with enalapril or rosuvastatin. Obesity (Silver Spring). 2008; 16(1):82-9. DOI: 10.1038/oby.2007.19. View

16.

Davidson E, Coppey L, Holmes A, Yorek M . Effect of inhibition of angiotensin converting enzyme and/or neutral endopeptidase on vascular and neural complications in high fat fed/low dose streptozotocin-diabetic rats. Eur J Pharmacol. 2011; 677(1-3):180-7. PMC: 3268870. DOI: 10.1016/j.ejphar.2011.12.003. View

17.

Kallinikos P, Berhanu M, ODonnell C, Boulton A, Efron N, Malik R . Corneal nerve tortuosity in diabetic patients with neuropathy. Invest Ophthalmol Vis Sci. 2004; 45(2):418-22. DOI: 10.1167/iovs.03-0637. View

18.

Calcutt N, Cooper M, Kern T, Schmidt A . Therapies for hyperglycaemia-induced diabetic complications: from animal models to clinical trials. Nat Rev Drug Discov. 2009; 8(5):417-29. PMC: 7097138. DOI: 10.1038/nrd2476. View

19.

Efron N, Edwards K, Roper N, Pritchard N, Sampson G, Shahidi A . Repeatability of measuring corneal subbasal nerve fiber length in individuals with type 2 diabetes. Eye Contact Lens. 2010; 36(5):245-8. DOI: 10.1097/ICL.0b013e3181eea915. View

20.

Tavakoli M, Kallinikos P, Iqbal A, Herbert A, Fadavi H, Efron N . Corneal confocal microscopy detects improvement in corneal nerve morphology with an improvement in risk factors for diabetic neuropathy. Diabet Med. 2011; 28(10):1261-7. PMC: 3181044. DOI: 10.1111/j.1464-5491.2011.03372.x. View