Pigment epithelium-derived factor in the vitreous is low in diabetic retinopathy and high in rhegmatogenous retinal detachment

doi:10.1016/S0002-9394(01)01008-X

American Journal of Ophthalmology

Volume 132, Issue 3, September 2001, Pages 378-382

https://doi.org/10.1016/S0002-9394(01)01008-X Get rights and content

Abstract

PURPOSE: To report the levels of pigment epithelium-derived factor in the vitreous of patients with diabetic retinopathy, rhegmatogenous retinal detachment, and idiopathic macular hole.

METHODS: Using enzyme-linked immunosorbent assay, we measured the levels of pigment epithelium-derived factor in the vitreous of 34 eyes of 33 patients who underwent vitrectomy for the treatment of diabetic retinopathy (17 eyes of 16 patients), rhegmatogenous retinal detachment (10 eyes), and idiopathic macular hole (seven eyes).

RESULTS: The vitreal concentration of pigment epithelium-derived factor was 1.15 ± 0.23 μg/ml (mean ± standard error) in eyes with diabetic retinopathy, 3.28 ± 0.69 μg/ml in rhegmatogenous retinal detachment, and 1.71 ± 0.39 μg/ml in idiopathic macular hole. The pigment epithelium-derived factor level in rhegmatogenous retinal detachment was significantly higher than that in diabetic retinopathy (P = .0008) and idiopathic macular hole (P = .034). For eyes with diabetic retinopathy, the pigment epithelium-derived factor level was 0.88 ± 0.21 μg/ml in proliferative diabetic retinopathy and 2.43 ± 0.37 μg/ml in nonproliferative diabetic retinopathy (P = .0083). Additionally, the pigment epithelium-derived factor level in active diabetic retinopathy (0.70 ± 0.22 μg/ml) was significantly lower than the level in inactive diabetic retinopathy (1.79 ± 0.35 μg/ml; P = .018).

CONCLUSIONS: These results suggest that pigment epithelium-derived factor inhibits angiogenesis and that lower levels of pigment epithelium-derived factor may be related to the angiogenesis in diabetic retinopathy and result in active proliferative diabetic retinopathy. The results also suggest that higher levels of pigment epithelium-derived factor in the eyes with rhegmatogenous retinal detachment may act as a neuroprotective agent for the detached retina.

Section snippets

Patients and methods

This study was conducted according to the tenets of the Declaration of Helsinki and was carried out after receiving approval from the institutional review committee of Kansai Medical University. After an explanation of the purpose of the experiment was presented, informed consent was obtained from all patients.

Undiluted vitreous samples were collected from 34 eyes of 33 individuals undergoing pars plana vitrectomy for the treatment of diabetic retinopathy and other retinal disorders at the

Results

The mean vitreous level of pigment epithelium-derived factor was 1.15 ± 0.23 μg/ml in eyes with diabetic retinopathy, 3.28 ± 0.69 μg/ml in eyes with rhegmatogenous retinal detachment, and 1.71 ± 0.39 μg/m in eyes with an idiopathic macular hole (Figure 1). The mean concentration of pigment epithelium-derived factor in eyes with diabetic retinopathy was significantly lower than the level in eyes with rhegmatogenous retinal detachment (P = .0008), and also lower than that in eyes with an

Discussion

Pigment epithelium-derived factor has been recently shown to inhibit neovascularization in rat corneas, to inhibit the proliferation of capillary endothelial cells, and to inhibit the migration of endothelial cells toward angiogenic inducers, such as platelet-derived factor and vascular endothelial growth factor.9 The vitreous humor has been shown to have antiangiogenic properties,13 and removal of pigment epithelium-derived factor from the vitreous fluid abrogates this antiangiogenic activity.

References (18)

J. Tombran-Tink et al.
PEDF. A pigment epithelium-derived factor with potent neuronal differentiative activity
Exp Eye Res
(1991)
S. Brem et al.
Inhibitor of neovascularization by an extract derived from vitreous
Am J Ophthalmol
(1977)
J. Tombran-Tink et al.
Neuronal differentiation of retinoblastoma cells induced by medium conditioned by human RPE cells
Invest Ophthalmol Vis Sci
(1989)
F.R. Steele et al.
Pigment epithelium-derived factorneurotrophic activity and identification as a member of the serine protease inhibitor gene family
Proc Natl Acad Sci USA
(1992)
T. Taniwaki et al.
Pigment epithelium-derived factor protects cultured cerebellar granule cells against glutamate-induced neurotoxicity
J Neurochem
(1997)
M.A. DeCoster et al.
Neuroprotection by pigment epithelium-derived factor (PEDF) on primary hippocampal neurons against glutamate toxicity
J Neurosci Res
(1999)
M.M. Jablonski et al.
Pigment epithelium-derived factor supports normal development of photoreceptor neurons and opsin expression after retinal pigment epithelium removal
J Neurosci
(2000)
J.G. McGinnis et al.
Retinal neurons in primary cell cultureinhibition of apoptosis by pigment epithelium-derived factor (PEDF)
Ogata N, Wang R, Jo N, et al. Pigment epithelium derived factor as a neuroprotective agent against ischemic retinal...

There are more references available in the full text version of this article.

Cited by (144)

The biological relevance of pigment epithelium-derived factor on the path from aging to age-related disease
2021, Mechanisms of Ageing and Development
Pigment epithelium-derived factor (PEDF) is an endogenously produced protein that contributes to cell growth arrest, and reduced levels of PEDF are associated with the progression of cellular senescence and the aging process. However, the mechanisms underlying PEDF regulation of these events are not completely clear. Increased PEDF activity may induce anti-aging processes, suggesting the potential therapeutic value of PEDF as an anti-aging and age-related disease. In this review, we recapitulate the molecular and cellular mechanisms of aging following the characteristics and specific roles of the PEDF in cell cycle arrest and its relevance to cellular senescence and aging pathways. In this context, the discovery and fluctuations of PEDF in age-related diseases are summarised. In light of the importance of PEDF in cellular senescence and aging processes, better comprehension of the mechanism(s) of PEDF in the regulation of cell cycle and the aging process can conceivably facilitate the development of therapeutic strategies for diseases that occur with aging.
Ischemic optic neuropathy as a model of neurodegenerative disorder: A review of pathogenic mechanism of axonal degeneration and the role of neuroprotection
2017, Journal of the Neurological Sciences
Optic neuropathy is a neurodegenerative disease which involves optic nerve injury. It is caused by acute or intermittent insults leading to visual dysfunction. There are number of factors, responsible for optic neuropathy, and the optic nerve axon is affected in all type which causes the loss of retinal ganglion cells. In this review we will highlight various mechanisms involved in the cell loss cascades during axonal degeneration as well as ischemic optic neuropathy. These mechanisms include oxidative stress, excitotoxicity, angiogenesis, neuroinflammation and apoptosis following retinal ischemia. We will also discuss the effect of neuroprotective agents in attenuation of the negative effect of factors involve in the disease occurrence and progression.
Low plasma levels of brain derived neurotrophic factor are potential risk factors for diabetic retinopathy in Chinese type 2 diabetic patients
2016, Molecular and Cellular Endocrinology
Previous studies suggested that neurotrophins play a role in the diabetic retinopathy (DR). We therefore evaluated the role of plasma brain derived neurotrophic factor (BDNF) levels in Chinese type 2 diabetic patients with and without diabetic retinopathy (DR). Plasma levels of BDNF were determined in type 2 diabetic patients (N = 344). At baseline, the demographical and clinical data were taken. Multivariate analyses were performed using logistic regression models. Receiver operating characteristic curves (ROC) was used to test the overall predict accuracy of BDNF and other markers. Diabetic patients with DR and vision-threatening diabetic retinopathy (VTDR) had significantly lower BDNF levels on admission (P < 0.0001 both). BDNF improved the area under the receiver operating characteristic curve of the diabetes duration for DR from 0.76 (95% confidence interval [CI], 0.71–0.82) to 0.89 (95% CI, 0.82–0.95; P < 0.01) and for VDTR from 0.84 (95% CI, 0.78–0.92) to 0.95 (95% CI, 0.90–0.98; P < 0.01). Multivariate logistic regression analysis adjusted for common risk factors showed that plasma BDNF levels≤12.4 ng/mL(1^rd quartiles) was an independent marker of DR (OR = 3.92; 95%CI: 2.31–6.56) and VTDR (OR = 4.88; 95%CI: 2.21–9.30). The present study demonstrated that decreased plasma levels of BDNF were independent markers for DR and VDTR in Chinese type 2 diabetic patients, suggesting a possible role of BDNF in the pathogenesis of DR complications.
Candidate SNP Markers Significantly Altering the Affinity of TATA-Binding Protein for the Promoters of Human Hub Genes for Atherogenesis, Atherosclerosis and Atheroprotection
2023, International Journal of Molecular Sciences
Sustained therapeutic effect of an anti-inflammatory peptide encapsulated in nanoparticles on ocular vascular leakage in diabetic retinopathy
2022, Frontiers in Cell and Developmental Biology
Neovascular Glaucoma
2022, Albert and Jakobiec's Principles and Practice of Ophthalmology: Fourth Edition

View all citing articles on Scopus

^☆: This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education in Japan.

View full text

Pigment epithelium-derived factor in the vitreous is low in diabetic retinopathy and high in rhegmatogenous retinal detachment☆

Abstract

Section snippets

Patients and methods

Results

Discussion

Exp Eye Res

Am J Ophthalmol

Neuronal differentiation of retinoblastoma cells induced by medium conditioned by human RPE cells

Invest Ophthalmol Vis Sci

Pigment epithelium-derived factorneurotrophic activity and identification as a member of the serine protease inhibitor gene family

Proc Natl Acad Sci USA

Pigment epithelium-derived factor protects cultured cerebellar granule cells against glutamate-induced neurotoxicity

J Neurochem

Neuroprotection by pigment epithelium-derived factor (PEDF) on primary hippocampal neurons against glutamate toxicity

J Neurosci Res

Pigment epithelium-derived factor supports normal development of photoreceptor neurons and opsin expression after retinal pigment epithelium removal

J Neurosci

Retinal neurons in primary cell cultureinhibition of apoptosis by pigment epithelium-derived factor (PEDF)