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The Pathogenesis and Therapeutic Strategies for Understanding and Treating Diabetic Neuropathy of the Retina

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 19816

Special Issue Editor

Dr. Toshiyuki Oshitari

E-Mail Website
Guest Editor
Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan
Interests: diabetic retinopathy; neuronal cell death; neurovascular units; axonal degeneration; glial changes; vascular abnormalities; neuroprotection; regeneration; optic coherence tomography; visual function
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

There is growing evidence that not only vascular abnormalities but also neuronal abnormalities, including retinal neuronal cell death, are associated with the pathogenesis of diabetic retinopathy. Neuronal cell death is an irreversible change and directly leads to vision loss in diabetic patients. In addition, numerous studies have demonstrated that retinal ganglion cell axons and dendrites are degenerated in the early stage of diabetes. The ultimate purpose of the therapies for patients with diabetic retinopathy is to protect their visual function by neuroprotection, axonal protection, and regeneration. However, the precise pathogenesis of diabetic neuropathy in the retina are still unclear. Diabetic retinopathy is a chronic retinal disease, and it is difficult to determine the pathogenesis of the onset and the progression of neuronal degeneration. Thus, some clues to determine the pathogenesis of the development and the progression of diabetic neuropathy in the retina must be obtained from other acute injury models such as ischemia and physical injury models. Therefore, in this Special Issue, we welcome articles from wide areas of neuroscience that are able to provide clues to determine the pathogenesis of diabetic neuropathy in the retina and to apply therapeutic strategies for the neuroprotection and regeneration of the neurons damaged by diabetic retinopathy.

Prof. Dr. Toshiyuki Oshitari
Guest Editor

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Keywords

  • diabetic retinopathy
  • neuronal cell death
  • neurovascular units
  • axonal degeneration
  • glial changes
  • vascular abnormalities
  • neuroprotection
  • regeneration
  • optic coherence tomography
  • visual function

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Published Papers (5 papers)

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Review

25 pages, 744 KiB  
Review
Current Treatments for Diabetic Macular Edema
by Tomoaki Tatsumi
Int. J. Mol. Sci. 2023, 24(11), 9591; https://doi.org/10.3390/ijms24119591 - 31 May 2023
Cited by 16 | Viewed by 5827
Abstract
Diabetic retinopathy is a major retinal disorder and a leading cause of blindness. Diabetic macular edema (DME) is an ocular complication in patients with diabetes, and it can impair vision significantly. DME is a disorder of the neurovascular system, and it causes obstructions [...] Read more.
Diabetic retinopathy is a major retinal disorder and a leading cause of blindness. Diabetic macular edema (DME) is an ocular complication in patients with diabetes, and it can impair vision significantly. DME is a disorder of the neurovascular system, and it causes obstructions of the retinal capillaries, damage of the blood vessels, and hyperpermeability due to the expression and action of vascular endothelial growth factor (VEGF). These changes result in hemorrhages and leakages of the serous components of blood that result in failures of the neurovascular units (NVUs). Persistent edema of the retina around the macula causes damage to the neural cells that constitute the NVUs resulting in diabetic neuropathy of the retina and a reduction in vision quality. The macular edema and NVU disorders can be monitored by optical coherence tomography (OCT). Neuronal cell death and axonal degeneration are irreversible, and their development can result in permanent visual loss. Treating the edema before these changes are detected in the OCT images is necessary for neuroprotection and maintenance of good vision. This review describes the effective treatments for the macular edema that are therefore neuroprotective. Full article
(This article belongs to the Special Issue The Pathogenesis and Therapeutic Strategies for Understanding and Treating Diabetic Neuropathy of the Retina)
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Figure 1

13 pages, 539 KiB  
Review
Visual Evoked Potentials for the Detection of Diabetic Retinal Neuropathy
by Gen Miura
Int. J. Mol. Sci. 2023, 24(8), 7361; https://doi.org/10.3390/ijms24087361 - 17 Apr 2023
Cited by 6 | Viewed by 2519
Abstract
Visual evoked potentials (VEP) are visually evoked signals that extract electroencephalographic activity in the visual cortex that can detect retinal ganglion cells, optic nerves, chiasmal and retrochiasmal dysfunction, including optic radiations, and the occipital cortex. Because diabetes causes diabetic retinopathy due to microangiopathy [...] Read more.
Visual evoked potentials (VEP) are visually evoked signals that extract electroencephalographic activity in the visual cortex that can detect retinal ganglion cells, optic nerves, chiasmal and retrochiasmal dysfunction, including optic radiations, and the occipital cortex. Because diabetes causes diabetic retinopathy due to microangiopathy and neuropathy due to metabolic abnormalities and intraneural blood flow disorders, assessment of diabetic visual pathway impairment using VEP has been attempted. In this review, evidence on the attempts to assess the visual pathway dysfunction due to abnormal blood glucose levels using VEP is presented. Previous studies have provided significant evidence that VEP can functionally detect antecedent neuropathy before fundus examination. The detailed correlations between VEP waveforms and disease duration, HbA1c, glycemic control, and short-term increases and decreases in blood glucose levels are evaluated. VEP may be useful for predicting postoperative prognosis and evaluating visual function before surgery for diabetic retinopathy. Further controlled studies with larger cohorts are needed to establish a more detailed relationship between diabetes mellitus and VEP. Full article
(This article belongs to the Special Issue The Pathogenesis and Therapeutic Strategies for Understanding and Treating Diabetic Neuropathy of the Retina)
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Figure 1

16 pages, 630 KiB  
Review
Optic Nerve Regeneration in Diabetic Retinopathy: Potentials and Challenges Ahead
by Suqian Wu and Xiaofen Mo
Int. J. Mol. Sci. 2023, 24(2), 1447; https://doi.org/10.3390/ijms24021447 - 11 Jan 2023
Cited by 3 | Viewed by 2670
Abstract
Diabetic retinopathy (DR), the most common microvascular compilation of diabetes, is the leading cause of vision loss and blindness worldwide. Recent studies indicate that retinal neuron impairment occurs before any noticeable vascular changes in DR, and retinal ganglion cell (RGC) degeneration is one [...] Read more.
Diabetic retinopathy (DR), the most common microvascular compilation of diabetes, is the leading cause of vision loss and blindness worldwide. Recent studies indicate that retinal neuron impairment occurs before any noticeable vascular changes in DR, and retinal ganglion cell (RGC) degeneration is one of the earliest signs. Axons of RGCs have little capacity to regenerate after injury, clinically leading the visual functional defects to become irreversible. In the past two decades, tremendous progress has been achieved to enable RGC axon regeneration in animal models of optic nerve injury, which holds promise for neural repair and visual restoration in DR. This review summarizes these advances and discusses the potential and challenges for developing optic nerve regeneration strategies treating DR. Full article
(This article belongs to the Special Issue The Pathogenesis and Therapeutic Strategies for Understanding and Treating Diabetic Neuropathy of the Retina)
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Figure 1

11 pages, 15410 KiB  
Review
Detecting Diabetic Retinal Neuropathy Using Fundus Perimetry
by Takayuki Baba
Int. J. Mol. Sci. 2021, 22(19), 10726; https://doi.org/10.3390/ijms221910726 - 3 Oct 2021
Cited by 6 | Viewed by 2362
Abstract
Fundus perimetry is a new technique for evaluating the light sense in the retina in a point-to-point manner. Light sense is fundamentally different from visual acuity, which measures the threshold for discriminating and perceiving two points or lines, called the minimum cognoscible. The [...] Read more.
Fundus perimetry is a new technique for evaluating the light sense in the retina in a point-to-point manner. Light sense is fundamentally different from visual acuity, which measures the threshold for discriminating and perceiving two points or lines, called the minimum cognoscible. The quality of measurement of retinal sensitivity has dramatically increased in the last decade, and the use of fundus perimetry is now gaining popularity. The latest model of fundus perimetry, MP-3, can be used for a wide range of measurements and has an advanced eye tracking system. High background illumination enables accurate measurement of mesopic retail sensitivity. Recent investigations have shown that neuronal damage precedes vascular abnormalities in diabetic retinopathy. The loss of retinal function has also been reported prior to morphological changes in the retina. In this review, the importance of measuring retinal sensitivity to evaluate visual function in the early stages of diabetic retinopathy was discussed. The usefulness of retinal sensitivity as an outcome measure in clinical trials for treatment modalities is also presented. The importance of fundus perimetry is promising and should be considered by both diabetes researchers and clinical ophthalmologists. Full article
(This article belongs to the Special Issue The Pathogenesis and Therapeutic Strategies for Understanding and Treating Diabetic Neuropathy of the Retina)
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17 pages, 2482 KiB  
Review
The Pathogenesis and Therapeutic Approaches of Diabetic Neuropathy in the Retina
by Toshiyuki Oshitari
Int. J. Mol. Sci. 2021, 22(16), 9050; https://doi.org/10.3390/ijms22169050 - 22 Aug 2021
Cited by 22 | Viewed by 5240
Abstract
Diabetic retinopathy is a major retinal disease and a leading cause of blindness in the world. Diabetic retinopathy is a neurovascular disease that is associated with disturbances of the interdependent relationship of cells composed of the neurovascular units, i.e., neurons, glial cells, and [...] Read more.
Diabetic retinopathy is a major retinal disease and a leading cause of blindness in the world. Diabetic retinopathy is a neurovascular disease that is associated with disturbances of the interdependent relationship of cells composed of the neurovascular units, i.e., neurons, glial cells, and vascular cells. An impairment of these neurovascular units causes both neuronal and vascular abnormalities in diabetic retinopathy. More specifically, neuronal abnormalities including neuronal cell death and axon degeneration are irreversible changes that are directly related to the vision reduction in diabetic patients. Thus, establishment of neuroprotective and regenerative therapies for diabetic neuropathy in the retina is an emergent task for preventing the blindness of patients with diabetic retinopathy. This review focuses on the pathogenesis of the neuronal abnormalities in diabetic retina including glial abnormalities, neuronal cell death, and axon degeneration. The possible molecular cell death pathways and intrinsic survival and regenerative pathways are also described. In addition, therapeutic approaches for diabetic neuropathy in the retina both in vitro and in vivo are presented. This review should be helpful for providing clues to overcome the barriers for establishing neuroprotection and regeneration of diabetic neuropathy in the retina. Full article
(This article belongs to the Special Issue The Pathogenesis and Therapeutic Strategies for Understanding and Treating Diabetic Neuropathy of the Retina)
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