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A synthetic tear protein resolves dry eye through promoting corneal nerve regeneration.

ABSTRACT: Corneal architecture is essential for vision and is greatly perturbed by the absence of tears due to the highly prevalent disorder dry eye. With no regenerative therapies available, pathological alterations of the ocular surface in response to dryness, including persistent epithelial defects and poor wound healing, result in lifelong morbidity. Here, using a mouse model of aqueous-deficient dry eye, we reveal that topical application of the synthetic tear protein Lacripep reverses the pathological outcomes of dry eye through restoring the extensive network of corneal nerves that are essential for tear secretion, barrier function, epithelial homeostasis, and wound healing. Intriguingly, the restorative effects of Lacripep occur despite extensive immune cell infiltration, suggesting tissue reinnervation and regeneration can be achieved under chronic inflammatory conditions. In summary, our data highlight Lacripep as a first-in-class regenerative therapy for returning the cornea to a near homeostatic state in individuals who suffer from dry eye.

SUBMITTER: Efraim Y

PROVIDER: S-EPMC9549932 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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A synthetic tear protein resolves dry eye through promoting corneal nerve regeneration.

Efraim Yael Y Chen Feeling Yu Ting FYT Cheong Ka Neng KN Gaylord Eliza A EA McNamara Nancy A NA Knox Sarah M SM

Cell reports 20220801 9

Corneal architecture is essential for vision and is greatly perturbed by the absence of tears due to the highly prevalent disorder dry eye. With no regenerative therapies available, pathological alterations of the ocular surface in response to dryness, including persistent epithelial defects and poor wound healing, result in lifelong morbidity. Here, using a mouse model of aqueous-deficient dry eye, we reveal that topical application of the synthetic tear protein Lacripep reverses the pathologic ...[more]

PMID: 36044852

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Project description:PurposeTo evaluate whether levels of corneal subbasal nerve fiber length (SNFL) in dry eye disease (DED) could prognosticate the level of improvement in signs and symptoms after treatment.DesignPhase IV, double-masked, randomized clinical trial.ParticipantsSixty patients with meibomian gland dysfunction-associated DED and 27 age-matched controls.MethodsPatients with DED were randomized to receive topical artificial tears, loteprednol etabonate 0.5%, or loteprednol etabonate 0.5%/tobramycin 0.3% twice daily for 4 weeks. At baseline, in vivo confocal microscopy of central cornea was performed in both eyes. Patients with DED were divided into 2 subgroups: those with low baseline SNFL and those with near-normal baseline SNFL for this purpose (the cutoff point: the mean SNFL in controls minus 2 standard deviations). Clinical signs and symptoms at baseline and after 4 weeks of treatment were compared between the subgroups with low and near-normal SNFL for all therapeutic groups.Main outcome measuresSymptom questionnaires, corneal fluorescein staining (CFS), conjunctival staining with lissamine green, tear break-up time, Schirmer's test, and SNFL.ResultsIn patients with DED, baseline SNFL (17.06±5.78 mm/mm(2)) was significantly lower than in controls (23.68±3.42 mm/mm(2), P = 0.001). In the artificial tear and loteprednol groups, although no significant improvement in any sign or symptom was noted in patients with low baseline SNFL (<16.84 mm/mm(2)), subjects with near-normal baseline SNFL (≥16.84 mm/mm(2)) showed significant improvement in both symptoms and CFS score (all P < 0.05). In the loteprednol/tobramycin group, no significant change was evident for any sign or symptom in either subgroup of low or near-normal baseline SNFL.ConclusionsSignificant improvements in CFS and patient symptomatology after DED treatment were evident only in the subgroup with near-normal corneal SNFL. Consideration of SNFL may assist in explaining the variability of patients' response to DED therapy.

Dataset Information

A synthetic tear protein resolves dry eye through promoting corneal nerve regeneration.

Publications

A synthetic tear protein resolves dry eye through promoting corneal nerve regeneration.

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