ISSN: 2455-1414

Journal of Clinical Research and Ophthalmology

Editorial       Open Access      Peer-Reviewed

Corneal Diabetes: Where to Next?

Karamichos Dimitrios*

Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA Department of Ophthalmology/Dean McGee Eye Research Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

Author and article information

*Corresponding author: Dimitrios Karamichos, Ph.D., Department of Ophthalmology, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Blvd, DMEI PA-409, Oklahoma City, OK 73104; Tel: 405-271-4019; E-mail: [email protected]
doi : 10.17352/2455-1414.000024
Submitted: 08 December, 2015 | Accepted: 08 December, 2015 | Published: 10 December, 2015
Keywords: Cornea; Diabetes; In vitro; In vivo

Cite this as

Dimitrios K (2015) Corneal Diabetes: Where to Next?. J Clin Res Ophthalmol. 2015; 2(4): 065-066. Available from: 10.17352/2455-1414.000024

Copyright License

© 2015 Dimitrios K. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Diabetes mellitus (DM) or better known as simply diabetes is a group of metabolic diseases in which high blood sugar levels are maintained over a prolonged period. Long term complications include but not limited to heart disease, stroke, kidney failure, and ocular damage. There are two main types of diabetes: Type I (T1DM) and Type II (T2DM). In 2013, an estimated 382 million people were diagnosed with diabetes with type 2 accounting for 90% of the cases. Unfortunately, to date, despite significant amount of research there is no known cure except in very specific cases.

DM was one of the first diseases described [1], with the first described cases believed to be T1DM. Originally, the disease was classified as “madhumeha” or “honey urine”[1], and was noted that urine attracts ants. The term diabetes was first used in 230 BCE and was considered as a rare disease. T1DM and T2DM were described and identified in 400-500 by Sushruta and Charaka [1], who associated T1DM with youth and T2DM with being overweight [1]. Today we know that T1DM is characterized by loss of the insulin-producing beta cells of the islets of Langerhans in the pancreas [2,3]. T2DM, on the other hand, is known for insulin resistance and it is the more common of the two [4,5].

Indexing and Abstracting

Editorial

Diabetes mellitus (DM) or better known as simply diabetes is a group of metabolic diseases in which high blood sugar levels are maintained over a prolonged period. Long term complications include but not limited to heart disease, stroke, kidney failure, and ocular damage. There are two main types of diabetes: Type I (T1DM) and Type II (T2DM). In 2013, an estimated 382 million people were diagnosed with diabetes with type 2 accounting for 90% of the cases. Unfortunately, to date, despite significant amount of research there is no known cure except in very specific cases.

DM was one of the first diseases described [1], with the first described cases believed to be T1DM. Originally, the disease was classified as “madhumeha” or “honey urine”[1], and was noted that urine attracts ants. The term diabetes was first used in 230 BCE and was considered as a rare disease. T1DM and T2DM were described and identified in 400-500 by Sushruta and Charaka [1], who associated T1DM with youth and T2DM with being overweight [1]. Today we know that T1DM is characterized by loss of the insulin-producing beta cells of the islets of Langerhans in the pancreas [2,3]. T2DM, on the other hand, is known for insulin resistance and it is the more common of the two [4,5].

With regards to ophthalmic complications as a result of DM, most profound effects are seen in cornea and retina. In fact, of the 382 million people diagnosed with DM worldwide approximately 70% of them suffer from some kind of corneal complications collectively and commonly known as diabetic keratopathy [6-10]. Common dysfunctions that may lead to impaired vision or blindness include decreased wound healing, corneal edema, and altered epithelial basement membrane. Clinically, we have no preventive measure for T1DM, while T2DM can be managed by means of physical exercise, weight control, and diet. Even then, the effect on the cornea will depend on the severity of the disease and the stage at which it was diagnosed. Unfortunately, DM is a chronic disease and corneal impairments are almost inevitable, mainly due to the fact that the eye has been exposed to hyperglycemia long-term and the basement membrane has accumulated enough toxic end products to lead to cell death, opacity, and eventually vision impairment.

In terms of research, in vivo, scientists have concentrated for years on animal studies and developed a variety of animal models both for T1DM [15-19] and T2DM [20-28], as recently reviewed by King [29]. However, there is a significant lack of reproducible paradigms of human DM complications and rather disappointing results when rodents' treatments are tested on humans. In vitro, there are quite a large number of studies looking into nerve pathologies and corneal sensitivity [9,11-14,30,31]. Perhaps the most advanced model is the organotypic cultures, developed by Ljubimov and co-authors [32,33], for the identification of epithelial defects in DM. Even still, we are way far from our ultimate goal which is to treat and prevent corneal damage and vision impairment.

In summary DM is a multifactorial disease and when it affects the human cornea there is a variety of factors that we have to consider if we are going to treat any defects. Clearly, both in vivo and in vitro studies are necessary and huge advancements have been made over the last ten years, but we need further and greater understanding of the molecular events at the initial stages of the disease.

References
  1. Poretsky L (2010) Principles of diabetes mellitus. 2nd ed. New York: Springer. 978-0-387-09841-8 .
  2. Lambert P, PJ Bingley (2002) What is Type 1 Diabetes? Medicine 30: 1-5.
  3. Rother KI (2007) Focus on research: Diabetes treatment - Bridging the divide. New England Journal of Medicine 356: 1499-1501.
  4. Shoback (2011) Greenspan's basic & clinical endocrinology G.G. David and Dolores, Editors. McGraw-Hill Medical: New York 85: 559.
  5. Riserus U, Willett WC, Hu FB (2009) Dietary fats and prevention of type 2 diabetes. Prog Lipid Res 48: 44-51.
  6. Skarbez K, Priestley Y, Hoepf M, Koevary SB (2010) Comprehensive Review of the Effects of Diabetes on Ocular Health. Expert Rev Ophthalmol 5: 557-577.
  7. Herse PR (1988) A review of manifestations of diabetes mellitus in the anterior eye and cornea. Am J Optom Physiol Opt 65: 224-230.
  8. Owen CG, Newsom RS, Rudnicka AR, Woodward EG (2005) Vascular response of the bulbar conjunctiva to diabetes and elevated blood pressure. Ophthalmology 112: 1801-1808 .
  9. Schultz RO, Peters MA, Sobocinski K, Nassif K, Schultz KJ (1981) Diabetic keratopathy. Trans Am Ophthalmol Soc 79: 180-199.
  10. Schultz RO, Matsuda M, Yee RW, Edelhauser HF, Schultz KJ (1984) Corneal endothelial changes in type I and type II diabetes mellitus. Am J Ophthalmol 98: 401-410.
  11. Dogru M, Katakami C, Inoue M (2001) Tear function and ocular surface changes in noninsulin-dependent diabetes mellitus. Ophthalmology 108: 586-592 .
  12. Yoon KC, Im SK, Seo MS (2004) Changes of tear film and ocular surface in diabetes mellitus. Korean J Ophthalmol. 18(2): p. 168-174.
  13. Schwartz DE (1974) Corneal sensitivity in diabetics. Arch Ophthalmol 91: 174-178.
  14. Rosenberg ME, Tervo TM, Immonen IJ, Muller LJ, Gronhagen-Riska C, et al. (2000) Corneal structure and sensitivity in type 1 diabetes mellitus. Invest Ophthalmol Vis Sci 41: 2915-2921.
  15. Nerup J, Mandrup-Poulsen T, Helqvist S, Andersen HU, Pociot F, et al. (1994) On the pathogenesis of IDDM. Diabetologia. 37 Suppl 2: p. S82-89.
  16. Yang Y, Santamaria P (2006) Lessons on autoimmune diabetes from animal models. Clin Sci (Lond) 110: 627-639.
  17. Lenzen S, Tiedge M, Elsner M, Lortz S, Weiss H et al (2001) The LEW.1AR1/Ztm-iddm rat: a new model of spontaneous insulin-dependent diabetes mellitus. Diabetologia 44: 1189-1196.
  18. Mathews CE, Langley SH, Leiter EH (2002) New mouse model to study islet transplantation in insulin-dependent diabetes mellitus. Transplantation 73: 1333-1336.
  19. Zhou CC, Pridgen B, King N, Xu J, Breslow JL (2011) Hyperglycemic Ins2(Akita)Ldlr(-/-) mice show severely elevated lipid levels and increased atherosclerosis: a model of type 1 diabetic macrovascular disease. J Lipid Res 52: 1483-1493.
  20. Yoshida S, Tanaka H, Oshima H, Yamazaki T, Yonetoku Y, et al. (2010) AS1907417, a novel GPR119 agonist, as an insulinotropic and beta-cell preservative agent for the treatment of type 2 diabetes. Biochem Biophys Res Commun 400: 745-751.
  21. Gault VA, Kerr BD, Harriott P, Flatt PR (2011) Administration of an acylated GLP-1 and GIP preparation provides added beneficial glucose-lowering and insulinotropic actions over single incretins in mice with Type 2 diabetes and obesity. Clin Sci (Lond) 121: 107-117.
  22. Park JS, Rhee SD, Kang NS, Jung WH, Kim HY (2011) Anti-diabetic and anti-adipogenic effects of a novel selective 11 beta-hydroxysteroid dehydrogenase type 1 inhibitor, 2-(3-benzoyl)-4-hydroxy-1,1-dioxo-2H-1,2-benzothiazine-2-yl-1-phenylethanone (KR-66344). Biochem Pharmacol 81:1028-1035 .
  23. Hummel KP, Dickie MM, Coleman DL (1966) Diabetes, a new mutation in the mouse. Science 153: 1127-1128.
  24. Phillips MS, Liu Q, Hammond HA, Dugan V, Hey PJ, et al. (1996) Leptin receptor missense mutation in the fatty Zucker rat. Nat Genet 13: 18-19.
  25. Clee SM, Attie AD (2007) The genetic landscape of type 2 diabetes in mice. Endocr Rev 28: 48-83.
  26. Ikeda H (1994) KK mouse. Diabetes Res Clin Pract 24: S313-316.
  27. Leiter EH, Reifsnyder PC (2004) Differential levels of diabetogenic stress in two new mouse models of obesity and type 2 diabetes. Diabetes 53: S4-11.
  28. Surwit RS, Kuhn CM, Cochrane C, McCubbin JA, Feinglos MN (1988) Diet-induced type II diabetes in C57BL/6J mice. Diabetes 37: 1163-1167.
  29. King AJF (2012) The use of animal models in diabetes research. British Journal of Pharmacology 166: 877-894.
  30. Hyndiuk RA, Kazarian EL, Schultz RO, Seideman S (1977) Neurotrophic corneal ulcers in diabetes mellitus. Arch Ophthalmol 95: 2193-2196.
  31. Xu KP, Li Y, Ljubimov AV, Yu FX (2009) High glucose suppresses epidermal growth factor receptor/phosphatidylinositol 3-kinase/Akt signaling pathway and attenuates corneal epithelial wound healing. Diabetes 58: 1077-1085.
  32. Kabosova A, Kramerov AA, Aoki AM, Murphy G, Zieske JD, et al. (2003) Human diabetic corneas preserve wound healing, basement membrane, integrin and MMP-10 differences from normal corneas in organ culture. Exp Eye Res 77: 211-217.
  33. Winkler MA, Dib C, Ljubimov AV, Saghizadeh M (2014) Targeting miR-146a to treat delayed wound healing in human diabetic organ-cultured corneas. PLoS One 9: e114692 .
 

Download as

Article Alerts

Subscribe to our articles alerts and stay tuned.


Creative Commons License This work is licensed under a Creative Commons Attribution 4.0 International License.

Help ?

Submit your next article Peertechz Publications, also join of our fulfilled creators. Submit a Manuscript

© Peertechz Publications Inc., 10880 Wilshire Blvd., Suite 1101, Los Angeles, California, 90024, USA