Drug Intervention Can Correct Subnormal Retinal Oxygenation Response in Experimental Diabetic Retinopathy

Berkowitz, Bruce A.; Roberts, Robin; Luan, Hongmei; Peysakhov, J.; Knoerzer, Deborah; Connor, Jane R.; Hohman, Thomas C.

doi:10.1167/iovs.05-0132

Cited by 50 publications

(58 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…interventionally). Importantly, we found that the success of two drug treatments at correcting abnormal DPO 2 when administered preventatively was not predictive of success when administered interventionally (60). Furthermore, a cyclo-oxygenase-2 inhibitor was found to reverse the abnormal DPO 2 when treatment was started after induction of the diabetes (60).…”

Section: Dpomentioning

confidence: 84%

See 1 more Smart Citation

Prognostic MRI biomarkers of treatment efficacy for retinopathy

Berkowitz

Roberts

2008

NMR in Biomedicine

Self Cite

View full text Add to dashboard Cite

There is a pressing need for retina-specific imaging biomarkers that robustly measure early (subclinical) changes in physiology, are linked to the histopathology responsible for vision loss, and, importantly, predict treatment efficacy. This review focuses on the following four MRI markers that we have developed and applied in preclinical and clinical settings: preretinal vitreous oxygen level (a steady-state biomarker of inner retinal oxygen tension); leakage of contrast agent into the vitreous (a steady-state biomarker of blood-retinal barrier permeability surface area product); change in preretinal vitreous oxygen tension during a hyperoxic provocation (a functional biomarker of vascular autoregulation); and retinal uptake of systemically administered manganese during a visual task (a functional biomarker of intraretinal ion regulation). We conclude that functional biomarkers are most promising for prognostic evaluation of treatment efficacy earlier in the course of retinopathy than is currently possible.

show abstract

Section: Dpomentioning

confidence: 84%

“…(b) A range of vasoactive drugs, including aminoguanidine, aldose reductase inhibitors, and inducible nitric oxide synthetase and cyclo-oxygenase-2 inhibitors, corrected abnormal retinal DPO 2 in experimental diabetic retinopathy (57,60). (c) Carbogen improves retinal oxygenation relative to pure O 2 breathing (20,61).…”

Section: Dpomentioning

confidence: 99%

Prognostic MRI biomarkers of treatment efficacy for retinopathy

Berkowitz

Roberts

2008

NMR in Biomedicine

Self Cite

View full text Add to dashboard Cite

show abstract

“…We found that mice lacking iNos were protected from the diabetes-induced production of nitric oxide, nitration of retinal proteins and, importantly, from the diabetes-induced degeneration of retinal capillaries. Previous research has demonstrated that inhibition of iNOS or iNos deficiency also inhibits development of early functional alterations in retinal oxygenation in diabetes [26,27].…”

Section: Discussionmentioning

confidence: 99%

Critical role of inducible nitric oxide synthase in degeneration of retinal capillaries in mice with streptozotocin-induced diabetes

et al. 2007

View full text Add to dashboard Cite

Aims/hypothesis Diabetes results in the upregulation of the production of several components of the inflammatory response in the retina, including inducible nitric oxide synthase (iNOS). The aim of this study was to investigate the role of iNOS in the pathogenesis of the early stages of diabetic retinopathy using iNOS-deficient mice (iNos −/− ). Materials and methods iNos −/− mice and wild-type (WT; C57BL/6J) mice were made diabetic with streptozotocin or kept as non-diabetic controls. Mice were killed at different time points after the induction of diabetes for assessment of vascular histopathology, cell loss in the ganglion cell layer (GCL), retinal thickness, and biochemical and physiological abnormalities. Results The concentrations of nitric oxide, nitration of proteins, poly(ADP-ribose) (PAR)-modified proteins, endothelial nitric oxide synthase, prostaglandin E 2 , superoxide and leucostasis were significantly (p<0.05) increased in retinas of WT mice diabetic for 2 months compared with nondiabetic WT mice. All of these abnormalities except PARmodified proteins in retinas were inhibited (p<0.05) in diabetic iNos −/− mice. The number of acellular capillaries and pericyte ghosts was significantly increased in retinas from WT mice diabetic for 9 months compared with nondiabetic WT controls, these increases being significantly inhibited in diabetic iNos −/− mice (p<0.05 for all). Retinas from WT diabetic mice were significantly thinner than those from their non-diabetic controls, whereas diabetic iNos −/− mice were protected from this abnormality. We found no evidence of cell loss in the GCL of diabetic WT or iNos −/− mice. Deletion of iNos had no beneficial effect on diabetes-induced abnormalities on the electroretinogram.Conclusions/interpretation We demonstrate that the inflammatory enzyme iNOS plays an important role in the pathogenesis of vascular lesions characteristic of the early stages of diabetic retinopathy in mice.

show abstract

“…Oxygen tension (in millimeters of mercury) in phantoms was measured by using an oxygen-sensitive fiberoptic probe (OxyLab; Oxford Q uantitative measurement of Po 2 in vivo could provide a clinically relevant indicator of oxygen concentration in the vitreous and the surrounding tissue, such as the retina, lens, and ciliary body. Abnormal vitreal oxygen tension has been linked to a number of ocular diseases, including cataract, diabetic retinopathy, and central retinal vein occlusion (1)(2)(3)(4). Vitrectomy (1,5) and hyperbaric oxygen therapy (6) have been associated with increased incidence of nuclear cataract, likely related to high vitreal Po 2 and reactive oxygen species contributing to cataract formation (7).…”

Section: Phantom and Ex Vivo Studiesmentioning

confidence: 99%

Human Vitreous: MR Imaging of Oxygen Partial Pressure

Muir¹,

Zhang²,

Nateras³

et al. 2013

Radiology

View full text Add to dashboard Cite

Purpose:To develop a magnetic resonance (MR) imaging approach to noninvasively image quantitative Po 2 in the human vitreous. Materials and Methods:Human studies were approved by the institutional review board with informed consent obtained from all subjects and were HIPAA compliant. Animal studies were performed with animal care committee approval. An MR imaging method to measure the longitudinal relaxation rate, or R1, of water was implemented with a 3.0-T MR imager. R1 was calibrated in water phantoms at multiple Po 2 and temperature conditions (n = 10) and in ex vivo animal vitreous (n = 2). Vitreous Po 2 was imaged in three human volunteers (age range, 26-28 years) in multiple sessions on separate days to evaluate reproducibility. The effects of temperature and ambient air were evaluated by acquiring data with the eye open and closed. Statistical analysis consisted of t tests, with P less than .05 indicating significant difference.

show abstract

Drug Intervention Can Correct Subnormal Retinal Oxygenation Response in Experimental Diabetic Retinopathy

Abstract: These results demonstrate, for the first time, that drug treatment can reverse an established subnormal DeltaPo2. Furthermore, this effect could not be predicted by a drugs' ability to prevent the development of subnormal DeltaPo2.

Cited by 50 publications

References 30 publications

Prognostic MRI biomarkers of treatment efficacy for retinopathy

Prognostic MRI biomarkers of treatment efficacy for retinopathy

Critical role of inducible nitric oxide synthase in degeneration of retinal capillaries in mice with streptozotocin-induced diabetes

Human Vitreous: MR Imaging of Oxygen Partial Pressure

Contact Info

Product

Resources

About