Retinal and Corneal Neurodegeneration and Their Association with Systemic Signs of Peripheral Neuropathy in Type 2 Diabetes

Häfner, Julia; Zadrazil, Markus; Grisold, Anna; Ricken, Gerda; Krenn, Martin; Kitzmantl, Daniela; Pollreisz, Andreas; Gleiß, Andreas; Schmidt‐Erfurth, Ursula

doi:10.1016/j.ajo.2019.09.010

Cited by 23 publications

(23 citation statements)

References 48 publications

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“…We observed a reduction in corneal fiber length and in branching points in diabetic mice of over 30%. Similar reductions in corneal nerve length and branchings have been previously reported using in vivo confocal microscopy [31][32][33]65]. Our study was not designed nor powered to determine whether diabetic nerve lengths differ from normal nerve lengths, whether the different diabetic mice types have different corneal nerve findings, or whether differences in corneal nerve lengths have any have physiological significance, however we do show a viable quantification approach that will lend this technology to future detailed study of diabetic disease on nerve density of the cornea.…”

Section: Discussionsupporting

confidence: 81%

“…It is possible that anatomical changes in the corneal nerves can precede physiological impairments, as confocal microscopy of corneal nerves can reveal diabetic nerve fiber damage earlier than corneal sensation testing and vibration perception assessment in the lower extremities [31]. Corneal nerve length has also been correlated with diabetic retinopathy with a statistically significant reduction in corneal nerve fiber length seen in diabetic patients with proliferative and non-proliferative retinopathy compared to diabetic patients with no diabetic retinopathy [32].…”

Section: Discussionmentioning

confidence: 99%

“…Confocal microscopy has been used extensively to investigate the corneal nerves in vivo [21][22][23][24][25][26][27][28][29][30], and in the context of studying the changes induced with diabetes mellitus on corneal nerves in humans, mice and rats [19,[31][32][33][34][35][36]. Patients with diabetes had reduced densities of major corneal nerves and nerve branching, as well as increased tortuosity [31,32]. Sub-basal layer corneal nerve density was reduced by over 30% in diabetic relative to control mice [33].…”

Section: Introductionmentioning

confidence: 99%

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In vivo imaging of corneal nerves and cellular structures in mice with Gabor-domain optical coherence microscopy

Canavesi

Cogliati

Mietus

et al. 2020

Biomed. Opt. Express

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Gabor-domain optical coherence microscopy (GDOCM) demonstrated in vivo corneal imaging with cellular resolution and differentiation in mice over a field of view of 1 mm 2 . Contact and non-contact imaging was conducted on six healthy and six hyperglycemic C57BL/6J mice. Cellular resolution in the 3D GDOCM images was achieved after motion correction. Corneal nerve fibers were traced and their lengths and branches calculated. Noncontact, label-free imaging of corneal nerves has clinical utility in health and disease, and in transplant evaluation. To the authors' knowledge, this is the first report of in vivo 3D corneal imaging in mice with the capability to resolve nerve fibers using a non-contact imaging modality.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In vivo imaging of corneal nerves and cellular structures in mice with Gabor-domain optical coherence microscopy

Canavesi

Cogliati

Mietus

et al. 2020

Biomed. Opt. Express

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show abstract

“…In previous reports, thinning of the retinal nerve fiber layer (RNFL) around the optic disc and partial thinning in ganglion cell complex around the fovea were observed with the progression of diabetic polyneuropathy 22,23 . Additionally, Hafner et al 24 . recently reported that the reduction of peripapillary retinal nerve fiber layer thicknesses was correlated with quantitative findings of small fiber neuropathy, i.e., intraepidermal nerve fiber density and findings in the corneal nerve fiber.…”

Section: Introductionmentioning

confidence: 92%

Alterations of retinal thickness measured by optical coherence tomography correlate with neurophysiological measures in diabetic polyneuropathy

Yamada

Himeno

Tsuboi

et al. 2020

J of Diabetes Invest

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Aims/Introduction Diabetic polyneuropathy (DPN) and diabetic retinopathy (DR) are traditionally regarded as microvascular complications. However, these complications may share similar neurodegenerative pathologies. Here we evaluate the correlations in the severity of DPN and changes in the thickness of neuroretinal layers to elucidate whether these complications exist at similar stages of progression. Materials and Methods A total of 43 patients with type 2 diabetes underwent a nerve conduction study (NCS), a macular optical coherence tomography, and a carotid artery ultrasound scan. Diabetic polyneuropathy was classified according to Baba’s classification using NCS. The retina was automatically segmented into four layers; ganglion cell complex (GCC), inner nuclear layer/outer plexiform layer (INL/OPL), outer nuclear layer/photoreceptor inner and outer segments, and retinal pigment epithelium (RPE). The thickness of each retinal layer was separately analyzed for the fovea and the parafovea. Results Fourteen patients were classified as having moderate to severe diabetic polyneuropathy. The thicknesses of the foveal and parafoveal INL/OPL increased in patients with diabetic polyneuropathy compared with patients without. The thickness of the parafoveal retinal pigment epithelium decreased in patients with diabetic polyneuropathy. The thinning of parafoveal ganglion cell complex and foveal and parafoveal retinal pigment epithelium were positively correlated with deterioration of nerve functions in the nerve conduction study, but the thickening of INL/OPL was positively correlated with the nerve function deterioration. The thinning of parafoveal ganglion cell complex and foveal retinal pigment epithelium were positively correlated with the thickening of the carotid intima‐media. Conclusions Depending on the progression of diabetic polyneuropathy, the ganglion cell complex and retinal pigment epithelium became thinner and the INL/OPL became thicker. These retinal changes might be noteworthy for pathological investigations and for the assessment of diabetic polyneuropathy and diabetic retinopathy.

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“…An increasing number of studies have indicated that the occurrence of retinal neurodegenerative changes in DR may be earlier than microvascular changes. Furthermore, both the proliferation of glial cells and the damage of photoreceptor cells may occur at the beginning of the disease ( 2 , 3 ). Most previous studies regarded DR as a vascular disease, but now comprehensive properties such as retinal neurodegeneration should also be considered ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

Kir4.1 may represent a novel therapeutic target for diabetic retinopathy (Review)

et al. 2021

Exp Ther Med

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As the major cause of irreversible loss of vision in adults, diabetic retinopathy (DR) is one of the most serious complications of diabetes. The imbalance of the retinal microenvironment and destruction of the blood-retinal barrier have a significant role in the progression of DR. Inward rectifying potassium channel 4.1 (Kir4.1) is located on Müller cells and is closely related to potassium homeostasis, water balance and glutamate clearance in the whole retina. The present review discusses the functions of Kir4.1 in regulating the retinal microenvironment and related biological mechanisms in DR. In the future, Kir4.1 may represent a novel alternative therapeutic target for DR through affecting the retinal microenvironment.

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Retinal and Corneal Neurodegeneration and Their Association with Systemic Signs of Peripheral Neuropathy in Type 2 Diabetes

Cited by 23 publications

References 48 publications

In vivo imaging of corneal nerves and cellular structures in mice with Gabor-domain optical coherence microscopy

In vivo imaging of corneal nerves and cellular structures in mice with Gabor-domain optical coherence microscopy

Alterations of retinal thickness measured by optical coherence tomography correlate with neurophysiological measures in diabetic polyneuropathy

Kir4.1 may represent a novel therapeutic target for diabetic retinopathy (Review)

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