A preliminary trial to determine whether prevention of dark adaptation affects the course of early diabetic retinopathy

Arden, G B; Gündüz, Metin; Kurtenbach, Anne; Völker, Michael; Zrenner, Eberhart; Gündüz, Şule; Kamış, Ümit; Öztürk, Bayram; Okudan, Süleyman

doi:10.1038/eye.2009.328

Cited by 40 publications

(44 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Results of a survey sent to a small group of diabetic patients who also had retinitis pigmentosa suggested that their diabetic retinopathy was less severe, presumably because of photoreceptor degeneration (13). In addition, Arden et al (22) conducted a study of 40 patients to determine if sleeping with one eye weakly illuminated with light (505 nm) to reduce the rod dark current could improve diabetes-induced macular edema of the retina. The authors reported that treatment with dim light kept rods light-adapted, and speculated that inhibition of the dark current was responsible for the reduction of defects in contrast sensitivity, tritan thresholds, and retinal edema in treated versus untreated eyes (23).…”

Section: Discussionmentioning

confidence: 99%

Photoreceptor cells are major contributors to diabetes-induced oxidative stress and local inflammation in the retina

Veenstra

Palczewski

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

267

268

View full text Add to dashboard Cite

Accumulating evidence suggests that photoreceptor cells play a previously unappreciated role in the development of early stages of diabetic retinopathy, but the mechanism by which this occurs is not clear. Inhibition of oxidative stress is known to inhibit the vascular lesions of early diabetic retinopathy, and we investigated whether the diabetes-induced oxidative stress in the retina emanates from photoreceptors. Superoxide generation was assessed in retinas of male C57BL/6J mice made diabetic for 2 mo (4 mo of age when killed) using histochemical (dichlorofluorescein and dihydroethidine) and bioluminescence (lucigenin) methods. Photoreceptors were eliminated in vivo by genetic (opsin −/− ) and chemical (iodoacetic acid) techniques. Immunoblots were used to measure expression of intercellular adhesion molecule 1 and the inducible form of nitric oxide synthase. Diabetes increased the generation of superoxide by diabetic mouse retina more at night than during the day. Photoreceptors were the major source of reactive oxygen species in the retina, and their deletion (either genetically in opsin −/− mice or acutely with iodoacetic acid) inhibited the expected diabetes-induced increase in superoxide and inflammatory proteins in the remaining retina. Both mitochondria and NADPH oxidase contributed to the observed retinal superoxide generation, which could be inhibited in vivo with either methylene blue or apocynin. Photoreceptors are the major source of superoxide generated by retinas of diabetic mice. Pharmaceuticals targeting photoreceptor oxidative stress could offer a unique therapy for diabetic retinopathy.T he pathogenesis of diabetic retinopathy remains unclear, but prior work by us and others has provided strong evidence in animal models that oxidative stress and inflammatory processes play important roles in the development of the vascular lesions characteristic of early stages of this retinopathy (1, 2). Inhibition of oxidative stress by feeding antioxidants or overexpressing antioxidant enzymes has reduced diabetes-induced degeneration of retinal capillaries (3-7). Moreover, oxidative stress has been reported to regulate expression of proinflammatory proteins (8-10), which also have been shown to play a critical role in the pathogenesis of this early retinopathy (2). However, which cells of the retina are the major sources of such oxidative stress in diabetes is unclear. In vitro studies of retinal endothelial cells or Müller cells incubated in elevated levels of glucose have demonstrated that these cells can contribute to oxidative stress (11, 12), but the contribution of other cell types and their relative importance has not been studied.Rod and cone photoreceptor cells are the most prevalent cells in the retina. These postmitotic cells have a very high metabolic rate, using more oxygen than other cells throughout the body. They are also considered as likely contributors to the eventual development of retinal hypoxia and subsequent neovascularization in advanced stages of diabetic retinopathy (13,14). Th...

show abstract

Section: Discussionmentioning

confidence: 99%

Photoreceptor cells are major contributors to diabetes-induced oxidative stress and local inflammation in the retina

Veenstra

Palczewski

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

267

268

View full text Add to dashboard Cite

show abstract

“…Consistent with this, daily photobiomodulation administered to a small series of diabetic patients having nonecenterinvolved macular edema was associated with the gradual reduction in retinal thickness. 95 Arden et al 98 likewise used light to exert a beneficial effect on DME. In one study, they used trans-eyelid retinal illumination of one eye in patients with DR during sleep throughout a 3-month period, and found a reduction in the number of hemorrhages and microaneurysms compared to the contralateral eyes.…”

Section: Photobiomodulationmentioning

confidence: 99%

“…In one study, they used trans-eyelid retinal illumination of one eye in patients with DR during sleep throughout a 3-month period, and found a reduction in the number of hemorrhages and microaneurysms compared to the contralateral eyes. 98 In another study by the same group, diabetic patients with early (nonesight-threatening) DME wore a mask that illuminated one closed eye with 505-nm light over 6 months while they slept. 57 This treatment likewise showed regression of DME and improved visual function.…”

Section: Photobiomodulationmentioning

confidence: 99%

Mechanistic Insights into Pathological Changes in the Diabetic Retina

Roy

Kern

Song

et al. 2017

The American Journal of Pathology

161

130

View full text Add to dashboard Cite

Increasing evidence points to inflammation as one of the key players in diabetes-mediating adverse effects to the neuronal and vascular components of the retina. Sustained inflammation induces biochemical and molecular changes, ultimately contributing to retinal complications and vision loss in diabetic retinopathy. In this review, we describe changes involving metabolic abnormalities secondary to hyperglycemia, oxidative stress, and activation of transcription factors, together with neuroglial alterations in the diabetic retina. Changes in biochemical pathways and how they promote pathophysiologic developments involving proinflammatory cytokines, chemokines, and adhesion molecules are discussed. Inflammation-mediated leukostasis, retinal ischemia, and neovascularization and their contribution to pathological and clinical stages leading to vision loss in diabetic retinopathy (DR) are highlighted. In addition, potential treatment strategies involving fibrates, connexins, neuroprotectants, photobiomodulation, and anti-inflammatory agents against the development and progression of DR lesions are reviewed. The importance of appropriate animal models for testing novel strategies against DR lesions is discussed; in particular, a novel nonhuman primate model of DR and the suitability of rodent models are weighed. The purpose of this review is to highlight our current understanding of the pathogenesis of DR and to summarize recent advances using novel approaches or targets to investigate and inhibit the retinopathy. (Am J Pathol 2017, 187: 9e19; http://dx

show abstract

“…6 A phase I clinical trial involving 12 patients with mild non-proliferative DR showed that trans-eyelid illumination of the retina during sleep was acceptable by patients, had no reported ill effects, and also improved DR and visual function. 26 In the light of this finding, we have conducted a further investigation on patients with early DMO. We hypothesised that DMO would be as susceptible to this intervention as had DR.…”

Section: Introductionmentioning

confidence: 99%

Regression of early diabetic macular oedema is associated with prevention of dark adaptation

Arden

Jyothi

Hogg

et al. 2011

Eye

Self Cite

View full text Add to dashboard Cite

Hypothesis Dark-adapted rods consume oxygen at high rates and light adaptation decreases this oxygen burden and can have therapeutic effects on diabetic macular oedema (DMO). Methods Patients with mild nonproliferative diabetic retinopathy (DR) and early, untreated non-sight-threatening DMO slept for 6 months wearing masks that illuminated the eyelid of one closed eye by 505 nm light. Exclusion criteria were any concomitant eye disease, DR 4ETDRS grade 35, and other systemic diseases. Primary outcome: change of OCT retinal thickness in the local region where oedema was present. Results A total of 34 out of 40 patients completed the study. Mean baseline OCT macular cube thickness was equivalent for study and fellow eyes. But study eyes had a greater mean thickness in the central subfield zone 1 (282±53 lm) vs (256±19 lm) the fellow eyes. Twenty-eight study eyes showed intraretinal cysts compared with nine in the fellow eyes. At 6 months, only 19 study eyes had cysts while cysts were seen in 20 fellow eyes. After 6 months, the worst affected ETDRS zone and the central subfield zone 1 reduced in thickness in study eyes only by 12 lm (95% CI 20 to À7, P ¼ 0.01). The secondary outcomes of change in visual acuity, achromatic contrast sensitivity, and microperimetric thresholds improved significantly in study eyes and deteriorated in fellow eyes. Conclusions Sleeping in dim light that can keep rods light adapted may reverse the changes of DMO.

show abstract

A preliminary trial to determine whether prevention of dark adaptation affects the course of early diabetic retinopathy

Cited by 40 publications

References 23 publications

Photoreceptor cells are major contributors to diabetes-induced oxidative stress and local inflammation in the retina

Photoreceptor cells are major contributors to diabetes-induced oxidative stress and local inflammation in the retina

Mechanistic Insights into Pathological Changes in the Diabetic Retina

Regression of early diabetic macular oedema is associated with prevention of dark adaptation

Contact Info

Product

Resources

About