Serum and Tear Levels of Nerve Growth Factor in Diabetic Retinopathy Patients

Park, Kyong Soo; Kim, Sung Soo; Kim, Jae Chan; Kim, Hyeon Chang; Im, Yong Sun; Ahn, Chul Woo; Lee, Hyung Keun

doi:10.1016/j.ajo.2007.11.011

Cited by 64 publications

(51 citation statements)

References 20 publications

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“…Until recently, our knowledge of the release of neurotrophins in diabetic tissue had been limited to techniques such as ELISA assays and quantitative measurement of mRNA expression that could not differentiate proNGF from mature NGF. We and others have reported significant increases of NGF levels in diabetic rat retinal ganglia and serum/tears of patients with diabetic retinopathy [1,6,7]. Recently, the development and availability of specific antibodies for proNGF and mature NGF have facilitated a better understanding of neurotrophin release under pathological conditions.…”

Section: Discussionmentioning

confidence: 99%

“…However, we and others have reported paradoxical increases in levels of NGF despite neuronal death in clinical and experimental diabetic retinopathy [1,6,7]. Our recent study described a mechanism of peroxynitrite-induced impairment of NGF signal via tyrosine nitration of tyrosine receptor kinase A (TrkA), the NGF survival receptor, and upregulation of p75 NTR (NTR is also known as NGFR), the neurotrophin receptor, causing retinal neurodegeneration in clinical and experimental diabetes [1].…”

Section: Introductionmentioning

confidence: 99%

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Diabetes-induced peroxynitrite impairs the balance of pro-nerve growth factor and nerve growth factor, and causes neurovascular injury

Al‐Gayyar²,

et al. 2010

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Aims/hypothesis Diabetic retinopathy, the leading cause of blindness in working-age Americans, is characterised by reduced neurotrophic support and increased proinflammatory cytokines, resulting in neurotoxicity and vascular permeability. We sought to elucidate how oxidative stress impairs homeostasis of nerve growth factor (NGF) and its precursor, proform of NGF (proNGF), to cause neurovascular dysfunction in the eye of diabetic patients. Methods Levels of NGF and proNGF were examined in samples from human patients, from retinal Müller glial cell line culture cells and from streptozotocin-induced diabetic animals treated with and without atorvastatin (10 mg/kg daily, per os) or 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato iron (III) chloride (FeTPPs) (15 mg/kg daily, i.p.) for 4 weeks. Neuronal death and vascular permeability were assessed by TUNEL and extravasation of BSA-fluorescein. Results Diabetes-induced peroxynitrite formation impaired production and activity of matrix metalloproteinase-7 (MMP-7), which cleaves proNGF extracellularly, leading to accumulation of proNGF and reducing NGF in samples from diabetic retinopathy patients and experimental models. Treatment of diabetic animals with atorvastatin exerted similar protective effects that blocked peroxynitrite using FeTPPs, restoring activity of MMP-7 and hence the balance between proNGF and NGF. These effects were associated with preservation of blood-retinal barrier integrity, preventing neuronal cell death and blocking activation of RhoA and p38 mitogen-activated protein kinase (p38MAPK) in experimental and human samples. Conclusions/interpretation Oxidative stress plays an unrecognised role in causing accumulation of proNGF, which can activate a common pathway, RhoA/p38MAPK, to mediate neurovascular injury. Oral statin therapy shows promise for treatment of diabetic retinopathy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Diabetes-induced peroxynitrite impairs the balance of pro-nerve growth factor and nerve growth factor, and causes neurovascular injury

Al‐Gayyar²,

et al. 2010

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“…LL-37 cathelicidin is an α-helix type AMP of the tear fluid mainly produced by the corneal epithelial cells. Similar to the defensins, cathelicidin exerts various antimicrobial [102] and immunomodulatory functions [54] Complement C4b [64] Brain-specific angiogenesis inhibitor 1-associated protein 2 [70] Lysozyme C [38] VEGF [56] Complement C9 [64] Cystathionine b-synthase [70] Lipophilin A [38] Complement factor B [64] MMP-13 [70] Immunoglobulin lambda chain [38] Pigment epithelial-derived factor [64] Podocan [70] Hsp27 [76] Interstitial retinol-binding protein [64] Selenoprotein P [70] β 2 -Microglobulin [76] Inter-α trypsin inhibitor heavy chain [64] Enolase [77] [95]. In addition, it has an important role in re-epithelialization during wound healing [107].…”

Section: The Chemical Barrier Of the Tears As A Possible Source For Bmentioning

confidence: 99%

“…Some of the proteins were identified as possible biomarkers for diabetic retinopathy, even if they may have not directly been implicated in the pathomechanism of DR. Significantly elevated levels of nerve growth factor, APOA1, lipocalin 1, lactotransferrin, lacritin, lysozyme C, lipophilin A and immunoglobulin lambda chain have been observed in PDR, while reduced level of lipocalin-1, hsp27, β 2 -microglobulin and increased levels of endothelin and neuron-specific enolase were shown in tears of patients with NPDR [38,[76][77][78][79]. There is high need for the identification of useful biomarkers for diagnosis and monitoring the progression of the DR, proteins which are able to distinguish between the patients without retinopathy, with non-proliferative and with proliferative stages of DR.…”

Section: Tear Proteomics As a Tool In Dr Specific Biomarker Studiesmentioning

confidence: 99%

“…In different studies various combinations of the patients groups are used. In general, the number of patients enrolled into each group is below 20; there are fewer studies carried out on higher number of patients [38,76]. Regarding the sample type used for biomarker studies, besides tears different biological fluids such as serum [79] and vitreous [80] were utilized.…”

Section: Tear Proteomics As a Tool In Dr Specific Biomarker Studiesmentioning

confidence: 99%

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Diabetic retinopathy: Proteomic approaches to help the differential diagnosis and to understand the underlying molecular mechanisms

Csősz

Deák

Kalló

et al. 2017

Journal of Proteomics

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a b s t r a c t a r t i c l e i n f oDiabetic retinopathy is the most common diabetic eye disease and a leading cause of blindness among patients with diabetes. The appearance and the severity of the symptoms correlate with the duration of diabetes and poor blood glucose level management. Diabetic retinopathy is also categorized as a chronic low-level inflammatory disease; the high blood glucose level promotes the accumulation of the advanced glycation end products and leads to the stimulation of monocytes and macrophages. Examination of protein level alterations in tears using state-of the art proteomics techniques have identified several proteins as possible biomarkers for the different stages of the diabetic retinopathy. Some of the differentially expressed tear proteins have a role in the barrier function of tears linking the diabetic retinopathy with another eye complication of diabetes, namely the diabetic keratopathy resulting in impaired wound healing. Understanding the molecular events leading to the eye complications caused by hyperglycemia may help the identification of novel biomarkers as well as therapeutic targets in order to improve quality of life of diabetic patients. Biological significance: Diabetic retinopathy (DR), the leading cause of blindness among diabetic patients can develop without any serious symptoms therefore the early detection is crucial. Because of the increasing prevalence there is a high need for improved screening methods able to diagnose DR as soon as possible. The non-invasive collection and the relatively high protein concentration make the tear fluid a good source for biomarker discovery helping the early diagnosis. In this work we have reviewed the administration of advanced proteomics techniques used in tear biomarker studies and the identified biomarkers with potential to improve the already existing screening methods for DR detection.

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Contact Lens Technology: From Fundamentals to Applications

Moreddu

Vigolo

Yetisen

2019

Adv Healthcare Materials

189

171

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Contact lenses are ocular prosthetic devices used by over 150 million people worldwide. Primary applications of contact lenses include vision correction, therapeutics, and cosmetics. Contact lens materials have significantly evolved over time to minimize adverse effects associated with contact lens wearing, to maintain a regular corneal metabolism, and to preserve tear film stability. This article encompasses contact lens technology, including materials, chemical and physical properties, manufacturing processes, microbial contamination, and ocular complications. The function and the composition of the tear fluid are discussed to assess its potential as a diagnostic media. The regulatory standards of contact lens devices with regard to biocompatibility and contact lens market are presented. Future prospects in contact lens technology are evaluated, with particular interest given to theranostic applications for in situ continuous monitoring the ocular physiology.

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Serum and Tear Levels of Nerve Growth Factor in Diabetic Retinopathy Patients

Cited by 64 publications

References 20 publications

Diabetes-induced peroxynitrite impairs the balance of pro-nerve growth factor and nerve growth factor, and causes neurovascular injury

Diabetes-induced peroxynitrite impairs the balance of pro-nerve growth factor and nerve growth factor, and causes neurovascular injury

Diabetic retinopathy: Proteomic approaches to help the differential diagnosis and to understand the underlying molecular mechanisms

Contact Lens Technology: From Fundamentals to Applications

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