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Biomedical subjects

Stephen C Pflugfelder

Publications and source records attributed to Stephen C Pflugfelder.

At least 55 records · Page 3Linked to original sources
PubMed2004

Corneal epitheliopathy of dry eye induces hyperesthesia to mechanical air jet stimulation.

PURPOSE: To evaluate corneal sensation in different groups: normal subjects, dry eye patients, and patients with and without dry eye after laser in situ keratomileusis (LASIK) using the modified Belmonte gas esthesiometer. DESIGN: A retrospective, clinic-based, case-control study. METHODS: We evaluated 20 normal subjects, 20 dry eye patients, 20 post-LASIK patients without dry eye, and six post-LASIK patients with dry eye. The corneal sensation was measured with the modified Belmonte gas esthesiometer that uses two different stimuli to assess mechanical and polymodal receptors on the corneal surface. Mechanoreceptors were assessed by 2-second pulsed air jets of variable intensity. Polymodal receptors were measured by stimulating the corneal with 2-second pulsed air jets of varying concentrations of CO(2), a gas that is converted to carbonic acid on contact with the corneal surface. The main outcome measure was determining corneal sensation. RESULTS: The mean +/- standard deviation (+/- SD) age was similar in all groups. The mean mechanical threshold was 61.50 +/- 20.07 ml/min in the normal group (n = 20), 34.60 +/- 21.09 ml/min in the dry group (n = 20, P <.05 vs normal), 99.50 +/- 47.40 ml/min in the post-LASIK group (n = 20, P <.01 vs normal), and 50.00 +/- 15.49 ml/min in the post-LASIK patients with keratitis sicca (n = 06, P <.05 vs post-LASIK). The percentage of CO(2) to elicit discomfort was similar in all groups (P >.05). No sex-related differences were noted (P >.05). There was a significant inverse correlation between the threshold of mechanical stimulation and the severity of corneal fluorescein staining. CONCLUSIONS: The Belmonte modified noncontact esthesiometer is a sophisticated instrument that can assess different types of corneal sensory receptors. Patients with dry eye were hypersensitive to the air jet stimulus of this instrument, and this appears to be due to altered corneal epithelial barrier function. Profound hypoesthesia was observed after LASIK and similar to dry eye, post-LASIK patients with dry eye were sensitized. These findings provide new insight into the hypersensitivity to environmental stresses, particularly air drafts experienced by dry eye patients.

Adult↗
PubMed2004

Inflammation in dry eye.

Dry eye is a condition of altered tear composition that results from a diseased or dysfunctional lacrimal functional unit. Evidence suggests that inflammation causes structural alterations and/or functional paralysis of the tear-secreting glands. Changes in tear composition resulting from lacrimal dysfunction, increased evaporation and/or poor clearance have pro-inflammatory effects on the ocular surface. This inflammation is responsible in part for the irritation symptoms, ocular surface epithelial disease, and altered corneal epithelial barrier function in dry eye. Anti-inflammatory therapies for dry eye target one or more of the inflammatory mediators/pathways that have been identified in dry eye.

Journal Article↗
PubMed2004

Recombinant human tumor necrosis factor receptor Fc fusion protein (Etanercept): experience as a therapy for sight-threatening scleritis and sterile corneal ulceration.

PURPOSE: To review the efficacy of Etanercept as an alternate therapy for treatment of necrotizing anterior scleritis and sterile corneal ulceration unresponsive to traditional therapies. METHODS: A retrospective review of 10 patients treated with Etanercept for vision-threatening scleritis and sterile corneal ulceration. RESULTS: Etanercept alone or in combination with other immunosuppressive therapies controlled inflammation, arrested tissue ulceration, and in many cases permitted tapering or cessation of toxic immunosuppressive therapies. No complications or systemic toxicity were observed with Etanercept use. CONCLUSION: Etanercept is an effective treatment for scleritis and sterile corneal ulceration and has a favorable benefit-to-risk ratio. It may be considered for therapy of progressive disease or cases that are unresponsive to traditional therapies.

Adult↗
PubMed2004

Mucous membrane pemphigoid in a patient with chronic lymphocytic leukemia.

PURPOSE: To describe a case of mucous membrane pemphigoid (MMP) with ocular manifestations in a patient subsequently diagnosed with B-cell chronic lymphocytic leukemia (CLL). METHODS: Case report and literature review. RESULTS: A 64-year-old man presented with redness and irritation of both eyes. The patient also had blistering lesions on the roof of his mouth, trunk, and buttocks as well as bilateral conjunctival ulceration and symblepharon formation. A complete blood count performed before initiating treatment of presumed mucous membrane pemphigoid revealed a markedly increased white blood cell count (83,920) with a predominance of lymphocytes. Hematologic evaluation including immunophenotyping flow cytometry resulted in the diagnosis of B-cell chronic lymphocytic leukemia. Cyclophosphamide treatment improved his MMP and decreased the white blood cell count. CONCLUSIONS: Mucous membrane pemphigoid has been reported in association with a variety of nonhematologic malignancies. This case suggests that mucous membrane pemphigoid may also occur in B-cell CLL and supports the concept that autoantibodies play a role in the pathogenesis of this cicatricial conjunctival disease.

Conjunctival Diseases↗
PubMed2004

Experimental dry eye stimulates production of inflammatory cytokines and MMP-9 and activates MAPK signaling pathways on the ocular surface.

PURPOSE: To evaluate whether experimentally induced dry eye in mice activates mitogen-activated protein kinase (MAPK) signaling pathways, c-Jun N-terminal kinases (JNK), extracellular-regulated kinases (ERK), and p38 and stimulates ocular surface inflammation. METHODS: 129SvEv/CD-1 mixed mice aged 6 to 8 weeks were treated with systemic scopolamine and exposure to an air draft for different lengths of time, from 4 hours to 10 days. Untreated mice were used as the control. The concentrations of IL-1beta and TNF-alpha in tear fluid washings and in corneal and conjunctival epithelia were measured by ELISA. MMP-9 in tear washings was evaluated by zymography, and gelatinase activity in the cornea and conjunctiva was determined by in situ zymography. Corneal and conjunctival epithelia were lysed in RIPA buffer for Western blot with MAPK antibodies, or they were lysed in 4 M guanidium thiocyanate solution for extraction of total RNA, which was used to determine gene expression by semiquantitative RT-PCR, real-time PCR, and gene array. RESULTS: Compared with those in age-matched control subjects, the concentrations of IL-1beta and MMP-9 in tear fluid washings and the concentrations of IL-1beta and TNF-alpha and gelatinolytic activity in the corneal and conjunctival epithelia were significantly increased in mice receiving treatments to induce dry eye after 5 or 10 days. The expression of IL-1beta, TNF-alpha, and MMP-9 mRNA by the corneal and conjunctival epithelia was also stimulated in mice treated for 5 or 10 days. The levels of phosphorylated JNK1/2, ERK1/2, and p38 MAPKs in the corneal and conjunctival epithelia were markedly increased as early as 4 hours after treatment, and they remained elevated up to 5 days. CONCLUSIONS: Experimental dry eye stimulates expression and production of IL-1beta, TNF-alpha, and MMP-9 and activates MAPK signaling pathways on the ocular surface. MAPKs are known to stimulate the production of inflammatory cytokines and MMPs, and they could play an important role in the induction of these factors that have been implicated in the pathogenesis of dry eye disease.

Animals↗
PubMed2004

Stimulation of matrix metalloproteinases by hyperosmolarity via a JNK pathway in human corneal epithelial cells.

PURPOSE: To investigate whether exposure of human corneal epithelial cells to hyperosmotic stress activates the c-Jun NH(2)-terminal kinase (JNK) stress-activated protein kinase (SAPK) pathway, and stimulates production of the matrix metalloproteinases (MMPs): gelatinase (MMP-9), collagenases (MMP-1 and -13), and stromelysin (MMP-3). METHODS: Primary human corneal epithelial cells cultured in normal osmolar medium (312 mOsM) were exposed to media with higher osmolarity (350-500 mOsM) achieved by adding NaCl, with or without SB202190, an inhibitor of the JNK pathway; dexamethasone; or doxycycline for different lengths of time. The conditioned media were collected after 24 hours of exposure for zymography and ELISA. Total RNA was extracted from cultures treated for 6 hours and subjected to semiquantitative RT-PCR. Cells treated for 5 to 60 minutes were lysed in RIPA buffer and subjected to Western blot with phospho (p)-specific antibodies against p-JNK and p-c-Jun. JNK1 activation was also detected with an immunoassay system. RESULTS: The concentrations of MMP-9, -1, and -3 proteins in 24-hour conditioned media of corneal epithelial cells progressively increased as the media's osmolarity was increased from 312 to 500 mOsM by the addition of NaCl. The concentration of MMP-13 progressively increased to a peak at 450 mOsM. Active p-JNK-1, p-JNK-2, and p-c-Jun were detected by Western blot as early as 5 minutes and peaked at 60 minutes in cells exposed to hyperosmolar media. The levels of p-JNK-1, p-JNK-2, and p-c-Jun correlated positively with the osmolarity of the culture media. The p-JNK inhibitor SB202190 and doxycycline markedly inhibited the stimulation of p-JNK-1, p-JNK-2, and p-c-Jun, as well as MMP-9, -1, -13, and -3 at both the mRNA and protein levels in the cells exposed to hyperosmolar media. CONCLUSIONS: Expression and production of MMP-9, -1, -13, and -3 by human corneal epithelial cells correlated positively with increasing media osmolarity. This increase was mediated at least in part through activation of the JNK SAPK pathway. Doxycycline, an agent used to treat MMP-mediated ocular surface disease, inhibited the hyperosmolarity-induced MMP production and JNK activation. The relevance of these findings to stimulated production of MMPs by the elevated tear osmolarity in dry eye remains to be determined.

Adolescent↗
PubMed2004

Characterization of putative stem cell phenotype in human limbal epithelia.

This study evaluated proposed molecular markers related to stem cell (SC) properties with the intention of characterizing a putative SC phenotype in human limbal epithelia. Human corneal and limbal tissues were cut in the vertical and horizontal meridians for histology, transmission electron microscopy (TEM), and immunostaining. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization were used to evaluate gene expression. TEM showed that the limbal basal cells were small primitive cells. Immunostaining disclosed that p63, ABCG2 and integrin alpha9 were primarily expressed by the basal epithelial cells of limbus. Antibodies against integrin beta1, epidermal growth factor receptor (EGFR), K19, enolase-alpha, and CD71 stained the basal cells of the limbus more brightly than the suprabasal epithelia. Integrin alpha6, nestin, E-cadherin and connexin 43 did not stain the limbal basal cells, but the suprabasal epithelia of the cornea and limbus showed strong immunoreactivity. K3 and involucrin stained only corneal and limbal superficial cells. RT-PCR showed higher levels of p63, ABCG2 and integrin alpha9 mRNA, but lower levels of K3, K12 and connexin 43 expressed in the limbal epithelia than the corneal epithelia. In situ hybridization showed that p63 transcripts were located in basal layer of the limbal epithelium. This work suggests that the basal epithelial cells of the limbus are p63, ABCG2 and integrin alpha9 positive, and nestin, E-cadherin, connexin 43, involucrin, K3, and K12 negative, with relatively higher expression of integrin beta1, EGFR, K19, and enolase-alpha. This putative SC phenotype may facilitate the identification and isolation of limbal epithelial SCs.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2003

Infectious keratitis after LASIK.

PURPOSE: To report the clinical course, management, and outcomes of culture-proven infectious keratitis in 15 eyes of 13 subjects after LASIK. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Fifteen eyes of 13 subjects who underwent LASIK and developed culture-positive keratitis. INTERVENTION: Infectious keratitis was encountered in the operative eyes between 1 day and 450 days. Cultures were obtained, and topical antibiotic therapy was administered in all cases. Some cases required flap lifting, irrigation, and soaking of the bed with antibiotics, flap amputation, or further surgical intervention. MAIN OUTCOME MEASURES: Time periods from onset to diagnosis, from clinical diagnosis to clinical resolution, final acuities, microbiologic profiles, and medical and surgical interventions were reviewed. RESULTS: Onset of symptoms of infection varied, depending on the infectious organism. Bacterial organisms tended to present earlier, whereas mycobacterial and fungal organisms had a later mean onset of presentation. Furthermore, the atypical organisms such as mycobacteria, fungus, and acanthamoeba also had a more delayed diagnosis, resulting in a prolonged disease course. CONCLUSIONS: Infectious keratitis after LASIK is a potentially vision-threatening complication. Onset of symptoms varies depending on causative agents. Furthermore, atypical organisms in the interface or beneath the flap can pose both diagnostic and therapeutic dilemmas. Location in the interface can make it more difficult to culture the organisms and prevent adequate penetration of topical antibiotics.

Adult↗
PubMed2003

Assessing the severity of keratitis sicca with videokeratoscopic indices.

PURPOSE: To determine the correlation between the regularity indices of the Tomey TMS-2N computerized videokeratoscopy (CVK) instrument (Tomey, Waltham, MA) with conventional measures of dry eye symptoms and disease. DESIGN: A retrospective, clinic-based, case-control study. PARTICIPANTS: A total of 16 eyes of 16 asymptomatic normal subjects and 74 eyes of 74 patients with reports of ocular irritation. METHODS: Corneal surface regularity and potential visual acuity indices of the Tomey TMS-2N CVK instrument were evaluated in patients with ocular irritation symptoms and in normal subjects. MAIN OUTCOME MEASURES: The surface regularity index (SRI), surface asymmetry index (SAI), potential visual acuity index (PVA), and irregular astigmatism index (IAI) of the Tomey TMS-2N were compared between normal and dry-eye patients. Severity of dry-eye symptoms was assessed with a validated questionnaire. Schirmer 1 test (without anesthesia), biomicroscopic meibomian gland evaluation with a composite severity score (MGD score), fluorescein tear break-up time (TBUT), and corneal fluorescein staining were performed. The correlations between CVK indices of the Tomey TMS-2N and the symptom severity score, Schirmer 1 test, MGD score, TBUT, and corneal fluorescein staining score were studied. RESULTS: Dry-eye patients had greater mean symptom severity scores, lower Schirmer 1 test scores, greater MGD scores, more rapid TBUT, and greater total corneal fluorescein staining scores (P < 0.001 for all parameters). The SRI, SAI, and IAI were all significantly greater in dry-eye patients than normal subjects. These were 0.46 +/- 0.36 (normal) versus 1.09 +/- 0.76 (dry) for the SRI (P = 0.0017), 0.30 +/- 0.15 (normal) versus 0.90 +/- 1.09 (dry) for the SAI (P = 0.0321), and 0.42 +/- 0.28 (normal) versus 0.56 +/- 0.24 (dry) for the IAI (P = 0.0321). The PVA index was significantly lower in the dry-eye patients (0.89 +/- 0.13) than normal eyes (0.68 +/- 0.23; P = 0.0008). The SRI, SAI, and IAI were positively correlated with total and central corneal fluorescein staining scores (P < 0.00001 for all indices). An SRI (> or =0.80), SAI (> or =0.50), and IAI (> or =0.50) had sensitivities in predicting total corneal fluorescein staining (score > or = 3) of 89%, 69%, and 82%, respectively. The specificity of these indices was 80%, 78%, and 82%, respectively. In all 90 eyes, the mean SRI was greater in subjects older than 50 years (P = 0.012) compared with younger patients, whereas no age effect was noted in the dry-eye patients. The SRI and PVA index showed better correlation with symptoms of blurred vision than the best-corrected visual acuity. CONCLUSIONS: Patients with ocular irritation have an irregular corneal surface that may contribute to their irritation and visual symptoms. Because of their high sensitivity and specificity, the regularity indices of the Tomey TMS-2N have the potential to be used as objective diagnostic indices for dry eye, as well as a means to evaluate the severity of this disease.

Adolescent↗
PubMed2003

Infectious keratitis after laser in situ keratomileusis: results of an ASCRS survey.

To investigate the incidence, culture results, treatment, and visual outcomes of infectious keratitis after laser in situ keratomileusis (LASIK) worldwide, the Cornea Clinical Committee of the American Society of Cataract and Refractive Surgery (ASCRS) contacted 8600 United States and international ASCRS members by e-mail and asked them to respond to a questionnaire about post-LASIK infectious keratitis. One hundred sixteen infections were reported by 56 LASIK surgeons who had performed an estimated 338 550 procedures. Seventy-six cases presented in the first week after surgery, 7 during the second week, 17 between the second and fourth weeks, and 16 after 1 month. Forty-seven cases were not diagnosed on initial presentation. The most common organisms cultured were atypical mycobacteria and staphylococci. Empiric therapy is not recommended as most of the organisms are opportunistic and not responsive to conventional therapy. Flap elevation and culturing should be performed when post-LASIK infectious keratitis is suspected.

Bacteria↗
PubMed2003

Anti-inflammatory therapy of dry eye.

As tear secretion and tear clearance decrease in the dry eye, an inflammatory response is initiated on the ocular surface that appears to involve both soluble and cellular mediators. Although the traditional approach to treating dry eye is to hydrate and lubricate the ocular surface with artificial tears, symptoms and/or sight-threatening corneal disease may persist in some patients on such aqueous enhancement therapies. In these patients, treatment with anti-inflammatory agents, such as cyclosporin A, corticosteroids, tetracyclines, or autologous serum, may be considered. Results of studies investigating the use of these agents are discussed. During treatment, patients should be conscientiously monitored for adverse effects.

Journal Article↗
PubMed2003

Management of the late ocular sequelae of Stevens-Johnson syndrome.

The acute conjunctivitis seen initially in Stevens-Johnson syndrome is followed by a cicatricial phase, which often leads to severe ocular surface disease and visual morbidity. Manifestations include keratinization of the conjunctiva, lid margins, and lacrimal and meibomian ducts, resulting in an unstable tear film and mechanical trauma to the conjunctiva and cornea with blinking. Limbal stem cell deficiency is the most vision-threatening sequela of Stevens-Johnson syndrome, as it causes corneal neovascularization, chronic corneal inflammation, and an irregular corneal epithelium. Management of late sequelae often requires a multipronged approach, including strategies for ocular surface protection, ocular surface support, and ocular surface reconstruction. In this review, established therapies, as well as new experimental therapies, are discussed.

Journal Article↗
PubMed2003

Keratoconus-like topographic changes in keratoconjunctivitis sicca.

PURPOSE: To describe a case of inferior corneal steepening with a keratoconus-like pattern in a patient with nocturnal lagophthalmos and aqueous tear deficiency (ATD). METHODS: Axial curvature mapping was performed with the Tomey TMS-2N videokeratoscopy instrument. Keratoconus-like topography patterns were identified with the Klyce Software package of this instrument. RESULTS: Axial videokeratoscopy showed asymmetric inferior corneal steepening in the right eye. The surface regularity index (SRI), surface asymmetry index (SAI), and the simulated keratometric cylinder change (CYL) were 1.05, 5.05, and 0.75, respectively. The keratoconus screening indices were as follows for the right eye: Klyce/Maeda index of 95% similarity (clinical keratoconus interpreted) and Smolek/Klyce index of 23.09% severity (keratoconus suspect interpreted). Ultrasound pachymetric mapping showed a normal central corneal thickness. We found a similar topographic pattern of keratoconus in seven eyes of 74 dry eye patients who were previously evaluated with the Tomey TMS-2N. CONCLUSION: Chronic ocular desiccation and aqueous tear deficiency can produce inferior corneal steepening and high astigmatism resembling keratoconus.

Adult↗
PubMed2003

Apoptosis of ocular surface cells in experimentally induced dry eye.

PURPOSE: To evaluate to effect of experimental dry eye on ocular surface apoptosis. METHODS: Aqueous tear production and clearance were inhibited by systemic administration of scopolamine and exposure to an air draft for 12 days in 4- to 6-week-old 129SvEv/CD-1 mixed white mice. Eyes and ocular adnexa were excised, cryosectioned, and evaluated for apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay, immunohistochemical assay for caspase-3 and poly(ADP-ribose) phosphate (PARP), and examination of nuclear morphologic changes by Hoechst DNA nuclear staining and transmission electron microscopy. RESULTS: The number of TUNEL-positive cells in the mice with induced dry eye was significantly increased compared with control mice in the following ocular regions: central corneal (P < 0.0014), peripheral corneal (P < 0.0001), bulbar conjunctival (P < 0.0021), and tarsal conjunctival (P < 0.0046) epithelia; tarsal conjunctival stroma (P < 0.0274); and lid margin (P < 0.0219, n = 4 in all cases). There were no significant differences observed between treated and control groups in the central corneal, peripheral corneal, or bulbar conjunctival stroma; meibomian glands; skin; retina-choroid; or episcleral regions. Immunohistochemistry for caspase-3 and poly(ADP-ribose) polymerase p85 fragment revealed increased immunoreactivity in regions of increased TUNEL positivity, particularly in the corneal and conjunctival epithelial cells. Ultrastructural morphologic changes consistent with apoptosis were observed in the conjunctival epithelial cells. CONCLUSIONS: Experimentally induced dry eye in mice causes apoptosis of cells in ocular surface tissues including the central and peripheral corneal epithelium, bulbar and tarsal conjunctival epithelia, tarsal conjunctival stroma, and lid margin. Apoptosis may play a key role in the pathogenesis of keratoconjunctivitis sicca and may be a therapeutic target for this condition.

Animals↗
PubMed2003

Regulated expression of collagenases MMP-1, -8, and -13 and stromelysins MMP-3, -10, and -11 by human corneal epithelial cells.

PURPOSE: This study investigated the regulated expression of collagenases (MMP-1, -8, and -13) and stromelysins (MMP-3, -10, and -11) by human corneal epithelial cells treated with IL-1 beta, TNF-alpha, and doxycycline, a medication used to treat ocular surface diseases. METHODS: Primary human corneal epithelial cell cultures were treated with IL-1 beta or TNF-alpha, with or without their corresponding inhibitors. Total RNA extracted from cells treated for 4 to 24 hours was subjected to semiquantitative RT-PCR and Northern hybridization. Conditioned media from 24-hour-treated cultures were evaluated for MMP production by ELISA and activity assays. RESULTS: Semiquantitative RT-PCR and Northern hybridization revealed that the mRNAs of MMP-1, -13, -3, -10, and -11 were dose dependently upregulated by IL-1 beta and TNF-alpha, whereas MMP-8 and -14 and tissue inhibitor of metalloproteinase (TIMP)-1 were not altered, in corneal epithelial cells. MMP ELISA and activity assays confirmed this dose-dependent increase in MMP-1, -13, -3, and -10 protein production in conditioned media by IL-1 beta and TNF-alpha. This stimulated production was inhibited by their neutralizing antibodies and by IL-1 receptor antagonist. Doxycycline suppressed stimulated MMP-1, -10, and -13 production at both the mRNA and protein levels. CONCLUSIONS: This study demonstrated that IL-1 beta and TNF-alpha upregulate collagenases (MMP-1, -13) and stromelysins (MMP-3, -10, and -11) in human corneal epithelial cells. Doxycycline suppresses stimulated MMP-1, -13, and -10 at the mRNA and protein levels, which suggests that collagenases and stromelysins may play a role in the pathogenesis of sterile corneal ulceration and other ocular surface diseases.

Blotting, Northern↗
PubMed2003

Neurturin-deficient mice develop dry eye and keratoconjunctivitis sicca.

PURPOSE: Neurturin has been identified as a neurotrophic factor for parasympathetic neurons. Neurturin-deficient (NRTN(-/-)) mice have defective parasympathetic innervation of their lacrimal glands. This study was conducted to evaluate tear function and ocular surface phenotype in NRTN(-/-) mice. METHODS: Determined by tail genomic DNA PCR, 25 NRTN(-/-) mice and 17 neurturin-normal (NRTN(+/+)) mice aged 6 weeks to 4 months were evaluated. Aqueous tear production, tear fluorescein clearance and corneal sensation were serially measured. Corneal permeability to AlexaFluor dextran (AFD; Molecular Probes, Eugene, OR) was measured by a fluorometric assay at 485 nm excitation and 530 nm emission. Histology was evaluated in PAS-stained sections. Mucin and HLA class II (IA) antigen were assessed by immunofluorescent staining. Tear IL-1beta was measured by ELISA, and tear matrix metalloproteinase (MMP)-9 by zymography. Gene expression in the corneal epithelia was analyzed by semiquantitative RT-PCR. RESULTS: In comparison to that in age-matched NRTN(+/+) mice, aqueous tear production, tear fluorescein clearance, and corneal sensation were significantly reduced in NRTN(-/-) mice, whereas corneal permeability to AFD was significantly increased. Immunoreactive MUC-4 and -5AC mucin and goblet cell density (P < 0.001) in the conjunctiva of NRTN(-/-) mice were lower than in NRTN(+/+) mice. The expression of MUC-1 and -4 mRNA by the corneal epithelium was reduced in NRTN(-/-) mice. There were a significantly greater number of IA antigen-positive conjunctival epithelial cells in NRTN(-/-) mice than NRTN(+/+) mice. Tear fluid IL-1beta and MMP-9 concentrations and the expression of IL-1beta, TNF-alpha, macrophage inflammatory protein (MIP)-2, cytokine-induced neutrophil chemoattractant (KC), and MMP-9 mRNA by the corneal epithelia were significantly increased in NRTN(-/-) mice, compared with NRTN(+/+) mice. CONCLUSIONS: Neurturin-deficient mice show phenotypic changes and ocular surface inflammation that mimic human keratoconjunctivitis sicca. This model supports the importance of a functional ocular surface-central nervous system-lacrimal gland sensory-autonomic neural network in maintaining ocular surface health and homeostasis.

Animals↗
PubMed2002

Dry eye and delayed tear clearance: "a call to arms.".

Dry eye may activate components of the ocular surface early warning system. Ocular surface stresses in dry eye, such as hyperosmolarity, could activate cellular stress pathways such as MAPKs. IL-1 and MMP-9 produced by the ocular surface epithelial cells may mediate initial events in the inflammatory cascade of dry eye through a dynamic interplay between them on the ocular surface.

Animals↗