NEURODEGENERATION AS AN EARLY SIGN OF DIABETIC RETINOPATHY

Authors

  • Nadia Artha Dewi Universitas Brawijaya
  • Muhammad Arfan Universitas Brawijaya
  • Herisa Rahmasari Universitas Brawijaya
  • Mutiara Kristiani Putri Universitas Brawijaya
  • Rulli Rosandi Universitas Brawijaya
  • Shahdevi Nandar Kurniawan Universitas Brawijaya

DOI:

https://doi.org/10.21776/ub.mnj.2022.008.01.12

Keywords:

Neurodegeneration, diabetic retinopathy, neurovascular unit, retinal nerve fiber layer, review

Abstract

Diabetic retinopathy is major cause of visual impairment and blindness in diabetic patients worldwide. The concept of diabetic retinopathy as vascular disease has established into not only microvascular complication but also neurodegeneration problems. Neurodegeneration plays an important role in pathogenesis of diabetic retinopathy. In fact, neuroretinal changes in diabetes can take place even before vasculopathy can be clinically detected.  This condition is marked by accelerated loss of neurons due to apoptosis, particularly in the inner retinal layer. The characteristic of neurodegeneration can be detected through retinal imaging and electrodiagnostics. This review is very crucial, because identifying the pathophysiology of diabetic neurodegeneration better, we may be able to provide interventions using the appropriate therapy. We may also be able to utilize these diagnostic tools  for early detections of diabetic retinopathy, thus preventing blindness due to diabetes.

Author Biographies

Nadia Artha Dewi, Universitas Brawijaya

Department of Ophthalmology

Muhammad Arfan, Universitas Brawijaya

Department of Ophthalmology

Herisa Rahmasari, Universitas Brawijaya

Department of Ophthalmology

Mutiara Kristiani Putri, Universitas Brawijaya

Department of Ophthalmology

Rulli Rosandi, Universitas Brawijaya

Department of Internal Medicine

Shahdevi Nandar Kurniawan, Universitas Brawijaya

Department of Neurology

References

Sasongko MB, Widyaputri F, Agni AN, Wardhana FS, Kotha S, Gupta P, et al. Prevalence of diabetic retinopathy and blindness in Indonesian adults with type 2 diabetes. American Journal of Ophthalmology; 2017. 181:79–87. DOI: 10.1016/j.ajo.2017.06.019

Wang W, Lo Amy CY. Diabetic retinopathy: Pathophysiology and treatment. International Journal of Molecular Science; 2018. 19,1816.

DOI: 10.3390/ijms19061816

Sam E Mansour, David J Browning, Keye Wong, Harry W Flynn Jr, Abdhish R Bhavsar. The evolving traetment of diabetic retinopathy. Clinical Ophthalmology; 2020. 14 653–678.

DOI: 10.2147/OPTH.S236637

Duh EJ, Sun JK, Stitt AW. Diabetic retinopathy: current understanding, mechanisms, and treatment strategies. JCI Insight; 2017. Jul;2(14).

DOI: 10.1172/jci.insight.93751

Lechner J, O'Leary OE, Stitt AW. The pathology associated with diabetic retinopathy. Vision research; 2017. Oct 1;139:7-14.

DOI: 10.1016/j.visres.2017.04.003

Simó R, Stitt AW, & Gardner TW. Neurodegeneration in diabetic retinopathy: Does it really matter?. Diabetologia; 2018. 61(9):1902-1912.

DOI: 10.1007/s00125-018-4692-1

Usui, Y. Elucidation of pathophysiology and novel treatment for diabetic macular edema derived from the concept of neurovascular unit. JMA Journal; 2020. 3(3):201-207. DOI: 10.31662/jmaj.2020-0022

Lynch SK, & Abrà moff MD. Diabetic retinopathy is a neurodegenerative disorder. Vision Research; 2017. 139:101-107. DOI: 10.1016/j.visres.2017.03.003

Barber AJ. Diabetic retinopathy: Recent advances towards understanding neurodegeneration and vision loss. Scienc China Life Science; 2015. 58:541–549. DOI: 10.1007/s11427-015-4856-x

Rashid K, Akhtar-Schaefer I, & Langmann T. Microglia in retinal degeneration. Frontiers in immunology; 1975. DOI: 10.3389/fimmu.2019.01975

Pillar S, Molsselev E, Sokolovska J, Grzybowski A. Recent development in diabetic retinal neurodegeneration: A literature review. Journal of Diabetes Research; 2020.

DOI: 10.1155/2020/5728674

Simó R, Hernández C, Neurodegeneration is an early event in diabetic retinopathy: Therapeutic implications. British Journal of Ophthalmology; 2012. 96:1285-1290. DOI: 10.1136/bjophthalmol-2012-302005

Barber AJ, Baccouche B. Neurodegeneration in diabetic retinopathy: Potential for novel therapies. Vision research; 2017. Oct 1;139:82-92.

DOI: 10.1016/j.visres.2017.06.014

Sohn EH, Van Dijk HW, Jiao C, Kok PH, Jeong W, Demirkaya N, & Abrà moff MD. Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus. Proceedings of the National Academy of Sciences; 2016. 113(19):E2655-E2664. DOI: 10.1073/pnas.1522014113

Elena Vecino, F David Rodriguez, Noelia Ruzafa, Xandra Pereiro, Sansar C Sharma. Glia–neuron interactions in the mammalian retina. Progress in Retinal and Eye Research; 2016. Volume 51, Pages 1-40. ISSN: 1350-9462.

DOI: 10.1016/j.preteyeres.2015.06.003.

Yun et al. Angiopoietin 2 induces astrocyte apoptosis via avβ5-integrin signaling in diabetic retinophaty. Journal Cell Death and Disease; 2016. Vol. 7, Pages 1-11. DOI: 10.1038/cddis.2015.347

Ramirez JM, Trivin A, et al. Immunohistochemical study of human retinal astroglia. Vision Research Journal; 1994. Vol.34. Page 1935-1946.

DOI: 10.1016/0042-6989(94)90024-8

Valverde AM, Miranda S, García-Ramírez M, González-Rodriguez Ã, Hernández C, & Simó R. Proapoptotic and survival signaling in the neuroretina at early stages of diabetic retinopathy. Molecular Vision; 2013. 19:47. Avalaible from: https://pubmed.ncbi.nlm.nih.gov/23335850/

Fu S, Dong S, Zhu M, Sherry D, Wang C, You Z, & Le YZ. Müller glia are a major cellular source of survival signals for retinal neurons in diabetes. Diabetes; 2013. 64(10), 3554-3563. DOI: 10.2337/db15-0180

Srinivasan S, Dehghani C, Pritchard N, Edwards K, Russell AW, Malik RA, & Efron N. Optical coherence tomography predicts 4-year incident diabetic neuropathy. Ophthalmic and Physiological Optics; 2017. 37(4):451–459. DOI: 10.1111/opo.12391

Gundogan FC, Akay F, Uzun S, Yolcu U, Cagiltay E, Toyran S. Early neurodegeneration of the inner retinal layers in type 1 diabetes mellitus. Ophthalmologica; 2016. 235(3):125–32. DOI: 10.1159/000442826

Loduca AL, Zhang C, Zelkha R, & Shahidi M. Thickness mapping of retinal layers by spectral-domain optical coherence tomography. American Journal Of Ophthalmology; 2010. 150(6):849-855. DOI: 10.1016/j.ajo.2010.06.034

Ctori I, & Huntjens B. Repeatability of foveal measurements using spectralis optical coherence tomography segmentation software. PloS One; 2015. 10(6). DOI: 10.1371/journal.pone.0129005

Scarinci Fabio, et al. Single retinal layer evaluation in patients with type 1 diabetes with no or early signs of diabetic retinopathy: The first hint of neurovascular crosstalk damage between neurons and capillaries? Ophthalmologica; 2017. 237(4):223-231.

DOI: 10.1159/000453551

Carpineto P, Toto L, Aloia R, Ciciarelli V, Borrelli E, Vitacolonna E, et al. Neuroretinal alterations in the early stages of diabetic retinopathy in patients with type 2 diabetes mellitus. Eye; 2016. 30(5):673–9. Avalaible from:

https://www.nature.com/articles/eye201613

Zafar Sidra et al. Retinal neurodegeneration as an early manifestation of diabetic eye disease and potential neuroprotective therapies. Current Diabetes Reports; 2019. 19(4):17. DOI: 10.1007/s11892-019-1134-5

Lakhani E, Wright T, Abdolell M, Westall C. Multifocal ERG defects associated with insufficient long-term glycemic control in adolescents with type 1 diabetes. Invest Ophthalmol Vision Science; 2010. 51(10):5297–303. DOI: 10.1167/iovs.10-5200

Heravian J, Ehyaei A, Shoeibi N, Azimi A, Ostadi-Moghaddam H, Yekta AA, et al. Pattern visual evoked potentials in patients with type II diabetes mellitus. J Ophthalmic Vision Res; 2012. 7(3):225–30.

Avalaible form:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520591/

Corduneanu Angela CV, Ciobanu Natalia, Groppa Stanislav. Evaluation of visual pathways using visual evoked potential in patients with diabetic retinopathy. Romanian Journal of Ophthalmology; 2019. 4:4. Avalaible from:

https://pubmed.ncbi.nlm.nih.gov/31915735/

Xiao-hong Wu, Jing-wen Fang, Yin-qiong Huang, Xue-feng Bai, Yong Zhuang, Xiao-yu Chen, Xia-hong Lin. Diagnostic value of optic disc retinal nerve fiber layer thickness for diabetic peripheral neuropathy. Journal of Zhejiang University-Science B (Biomedicine & Biotechnology); 2020. 21(11):911-920. DOI: 10.1631/jzus.B2000225

Hafner J, Zadrazil M, Grisold A, Ricken G, KrennM, Kitzmantl D, et al. Retinal and corneal neurodegeneration and its association to systemic signs of peripheral neuropathy in type 2 diabetes. American Journal of Ophthalmology; 2020. 209:197-205.

DOI: 10.1016/j.ajo.2019.09.010.

Downloads

Published

2022-01-01

Issue

Section

Review