Topical 0.1% Prednisolone Lowers Nerve Growth Factor Expression in Keratoconjunctivitis Sicca Patients

Lee, Hyung Keun; Ryu, Ik Hee; Seo, Kyoung Yul; Hong, Suk Ki; Kim, Hyung Chang; Kim, Eung Kweon

doi:10.1016/j.ophtha.2005.09.033

Cited by 82 publications

(66 citation statements)

References 27 publications

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“…NGF signaling favors limbal epithelial stem cell survival and phenotype preservation on amniotic membranes (Touhami et al, 2002). Increased NGF levels were observed in KCS patient tears and ocular surfaces (Lee et al, 2006b). The mechanism by which NGF is elevated in KCS and its exact role in ocular surface dryness are undetermined.…”

Section: Discussionmentioning

confidence: 97%

“…KCS induces pathological changes by hyperosmolar stress in the corneal epithelium, including increased desquamation, disrupted intercellular connections, microplicae blunting and loss, cell membrane disruption, and cellular swelling with decreased cytoplasmic density (Gilbard et al, 1984;Luo et al, 2005). We previously found that NGF levels were elevated in tears from KCS patients, and that these levels decreased after treatment with anti-inflammatory corticosteroids (Lee et al, 2006b). These findings suggest another role for NGF in corneal epithelium linking hyperosmotic stress and proinflammatory cytokine production.…”

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confidence: 99%

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The role of nerve growth factor in hyperosmolar stress induced apoptosis

Chang

Kay

et al. 2008

Journal Cellular Physiology

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Nerve growth factor (NGF) is a neurotrophic factor that plays an important role in the differentiation and growth of neuronal cells. It is also regarded as an inflammatory mediator in non-neuronal tissues under physiological stress conditions. The mechanisms of NGF production and its roles in hyperosmolar stress conditions have not been established. In this study, we show that NGF levels in cultured human corneal epithelial cells (HCECs) were up-regulated during hyperosmolar stress by IL-1beta, but not TNF-alpha. NF-kappaB activity, but not AP-1, increased significantly under hyperosmolar conditions, and NF-kappaB was involved in IL-1beta-induced NGF production. IL-1beta-induced NGF production reduced JNK phosphorylation and HCEC apoptosis. These changes were accompanied by down-regulated Bax and caspase-3, -8, -9 activities. NGF siRNA and the tyrosine kinase inhibitor K252a significantly enhanced Bax up-regulation. Thus, up-regulated NGF under hyperosmolar stress conditions may contribute, at least in part, to reduced HCEC apoptosis. This conclusion suggests that enhanced NGF expression may be beneficial in recovering corneal damage due to chronic hyperosmolar stress.

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Section: Discussionmentioning

confidence: 97%

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confidence: 99%

The role of nerve growth factor in hyperosmolar stress induced apoptosis

Chang

Kay

et al. 2008

Journal Cellular Physiology

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“…Steroids may help increase goblet cell density and reduce the accumulation of inflammatory cells within ocular surface tissues (Avunduk et al, 2003;Pflugfelder et al, 2004). Lee et al(2006) and others reported ocular surface nerve growth factor (NGF) may play an important role in ocular surface inflammation processes associated with dry eye. Keratoconjunctivitis sicca patients showed elevated levels of tear NGF, which were decreased by treatment with 0.1% prednisolone.…”

Section: Discussionmentioning

confidence: 99%

A clinical study of the efficacy of topical corticosteroids on dry eye

Yang

Sun

2006

J. Zhejiang Univ. - Sci. B

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Abstract:Objective: To evaluate the effect of topical corticosteroid for treatment of moderate or severe dry eye. Methods: Sixty eyes of 30 patients with moderate or severe dry eye, who were not sensitive to artificial tears, were treated with 0.1% fluorometholone eye drops. Subjective symptom and objective tests were used to evaluate the efficacy of treatment before and after application of 0.1% fluorometholone eye drops for 1 week and 1 month. Side effects were also evaluated. Results: After 1 week of treatment, subjective symptoms were improved in all dry eye patients; objective tests were improved in all dry eye patients 1 month after treatment, and the difference was significant. Conclusion: Topical corticosteroid drops can rapidly and effectively relieve the symptoms and signs of moderate or severe dry eye.

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“…The total protein concentration of each corneal sample was measured using the micro-bovine serum albumin method to calculate the ratio of cytokine to total corneal protein. 25 The SPR data were analyzed by ProteOn Manager Software. * Association kinetic constant.…”

Section: Luminex Assay For Measuring Cytokines Concentrationmentioning

confidence: 99%

Neutralization of Ocular Surface TNF-α Reduces Ocular Surface and Lacrimal Gland Inflammation Induced by In Vivo Dry Eye

Byun

Choi

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The purpose of this study was to investigate the effectiveness of tumor necrosis factor (TNF)-a blocker for treatment of dry eye (DE)-induced inflammation and determine a more effective method to suppress lacrimal gland inflammation. Efficacy of topical versus systemic administration of TNF-a blockers was determined using a murine dry eye (DE) model. METHODS.The TNF-a blocker HL036 was developed by modification of the TNF receptor I. Protein purity, binding affinity, and clearance of TNF-a was compared with etanercept. Using DE-induced C57BL/6 mice, corneal erosion and goblet cell counts were measured after subcutaneous or topical treatment with etanercept or HL036. Inflammatory cytokines in cornea and lacrimal glands were determined by quantitative RT-PCR and ELISA.RESULTS. HL036 showed TNF-a binding affinity comparable to etanercept, as measured by surface plasmon resonance. HL036 concentration was significantly higher in cornea and anterior segment than etanercept and effectively eliminated TNF-a on ocular surfaces. Etanercept was preferentially concentrated in the posterior segment. Corneal erosion and goblet cell counts were improved only with topically applied etanercept and HL036. Ocular surface IFN-c, IL-6, and IL-21 were significantly decreased by topical HL036. DE-induced lacrimal gland IFN-c and IL-6 expression was effectively suppressed by topical etanercept and HL036.CONCLUSIONS. Topical TNF-a blockers effectively suppressed lacrimal gland and corneal inflammation by suppressing IFN-c, IL-21, and IL-6. Differences in TNF-a affinity, clearance, and local concentration of blockers may account for the anti-inflammatory effects in different ocular regions.

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Topical 0.1% Prednisolone Lowers Nerve Growth Factor Expression in Keratoconjunctivitis Sicca Patients

Cited by 82 publications

References 27 publications

The role of nerve growth factor in hyperosmolar stress induced apoptosis

The role of nerve growth factor in hyperosmolar stress induced apoptosis

A clinical study of the efficacy of topical corticosteroids on dry eye

Neutralization of Ocular Surface TNF-α Reduces Ocular Surface and Lacrimal Gland Inflammation Induced by In Vivo Dry Eye

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