Carnosine decreases retinal ganglion cell death in a mouse model of optic nerve crushing.

PURPOSE: The objectives of this study were to investigate whether carnosine can increase retinal ganglion cell (RGC) survival in the mouse retina and to determine the possible association between nuclear factor-kappa B (NF-κB) mediated oxidative stress and neuroprotection of RGCs following optic nerve crushing (ONC). METHODS: C57BL/6 J mice underwent ONC and were treated with carnosine (250 mg/kg) or saline intraperitoneally once daily until sacrifice. Peroxisome proliferator activated receptor (PPAR)-γ and glial fibrillary acidic protein (GFAP) expression were assessed at 1, 3, and 7 days after ONC. The effects of carnosine on the expression of PPAR-γ, GFAP, and NF-κB were assessed. To evaluate the effects of carnosine on mitochondrial biogenesis and function, we compared the expression of PPAR gamma coactivator-1α (PGC-1α) and mitochondrial transcription factor A (mtTFA) in retinas from mice that were treated with carnosine or saline at 3 days after ONC. RGC survival was assessed by labeling flat-mounted retinas with Brn3a at 2 weeks after ONC. RESULTS: The expression levels of PPAR-γ and GFAP were upregulated in saline-treated retinas for 7 days after ONC, with maximal expression at 3 days, and carnosine treatment effectively attenuated this upregulation. In addition, upregulation of NF-κB, PGC-1α and mtTFA expression was also observed in saline-treated retinas after ONC, and this upregulation was blocked by carnosine treatment, resulting in a significant difference between carnosine-treated and saline-treated retinas after ONC. Immunohistochemical staining for Brn3a also showed that carnosine treatment protected against RGC loss after ONC. CONCLUSIONS: Inhibition of NF-κB expression and oxidative stress by carnosine treatment plays a significant role in the prevention of RGC loss after ONC. The results also highlight the potential of carnosine as a neuroprotective agent against RGC loss in optic neuropathy.

Clinical validity of macular ganglion cell complex by spectral domain-optical coherence tomography in advanced glaucoma.

PURPOSE: To evaluate the repeatability and diagnostic power of macular ganglion cell complex (mGCC) thickness and peripapillary retinal nerve fiber layer (pRNFL) thickness using a spectral domain-optical coherence tomography in advanced glaucoma. PATIENTS AND METHODS: Forty advanced glaucoma patients were enrolled. Patients were divided into 2 groups of 20 patients each, according to the MD between -20 and -10 dB, and <-20 dB. The thickness of mGCC and pRNFL were measured with spectral domain-optical coherence tomography in both the groups. The repeatability of each parameter was assessed in both the groups, and the diagnostic power of each parameter was compared with the normal controls. RESULTS: Comparison of diagnostic power between the pRNFL and mGCC parameters revealed that the area under the receiver operating characteristic curve was not significantly different in patients with advanced glaucoma. The repeatability of pRNFL parameters was similar, irrespective of the severity of glaucoma. However, the repeatability of mGCC parameters became lower as the severity increased in patients with advanced glaucoma. CONCLUSIONS: In advanced glaucoma, the measurement of mGCC thickness has similar diagnostic power as the measurement of pRNFL thickness. However, the measurement of mGCC thickness showed a lower repeatability as MD decreased.

Experimental chronic ocular hypertension by anterior chamber injection of 0.3% carbomer solution in the rat.

BACKGROUND: To evaluate a chronic ocular hypertensive model by anterior chamber injection of 0.3% carbomer solution in rats. METHODS: Chronic ocular hypertension was induced unilaterally by injecting 20 µL of 0.3% carbomer solution into the anterior chamber in 3-month-old Sprague Dawley rats. Intraocular pressure was measured everyday for 1 week and then every week for 2 months after a single or repeated injection. Retinal ganglion cell loss was assessed quantitatively using FluoroGold labelling at 2, 4 and 8 weeks after injection. Anterior chamber angle and optic nerve were examined after chronic intraocular pressure elevation. RESULTS: The mean and peak intraocular pressure of the injected eyes were elevated significantly higher than those of the control eyes for 6 weeks of the experiment, after a single injection of carbomer solution and a second injection at 2 weeks resulted in an 8-week elevation of the mean and peak intraocular pressure, which was significantly higher than those of the control eyes. Elevated intraocular pressure induced retinal ganglion cell loss by approximately 21%, 27% and 38% compared with that in the control eyes at 2, 4 and 8 weeks, respectively, after a single injection. In carbomer-injected eyes with chronic intraocular pressure elevation, the obstruction of anterior chamber angle by peripheral anterior synechia and optic nerve degeneration were observed. CONCLUSIONS: Anterior chamber injection of 0.3% carbomer solution was an effective and reproducible method to produce chronic intraocular pressure elevation and glaucomatous neurodegeneration in rats.

Selectively bonded polymeric glaucoma drainage device for reliable regulation of intraocular pressure.

A novel glaucoma drainage device (GDD) using a polymeric micro check valve with no reverse flow is presented for the effective regulation of intraocular pressure (IOP). A significant functional improvement was achieved by reducing the possible incidence of hypotony, as the proposed GDD only drains aqueous humor at a certain cracking pressure or higher. The device consists of three biocompatible polymer layers: a top layer (cover), an intermediate layer (membrane), and a bottom layer (base plate with a cannula). All three layers, made of soft polydimethylsiloxane (PDMS), were bonded together to realize the thin GDDs. The bottom layer was selectively coated with chromium (Cr)/gold (Au) to prevent stiction between the valve seat and the valve orifice so that the device could show enhanced reliability in operation and high yield in production. Two types of polymeric devices were fabricated; one was a glaucoma drainage device for humans (GDDH) and the other was a glaucoma drainage device for animals (GDDA). From subsequent in vitro tests, the cracking pressures were 18.33 ± 0.66 mmHg (mean ± standard deviation) for GDDH and 12.42 mmHg for GDDA, both of which were very close to the corresponding normal IOPs. From in vivo tests of GDDA, the IOP of all implanted devices was properly regulated within the target pressure (10-15 mmHg). The experimental results showed that the proposed polymeric GDD has high potential for use in the treatment of glaucoma disease in terms of its repeatability of the cracking pressure and patients' relief from post-operative discomfort.

Usefulness of double vital staining with 1% fluorescein and 1% lissamine green in patients with dry eye syndrome.

PURPOSE: To determine the relative staining characteristics of the nasal and temporal conjunctiva as compared with other measures of dry eye and evaluate the qualitative clinical impression of the utility of the double vital staining with fluorescein and lissamine green. METHODS: Ocular surface staining was performed with a mixture of 1% fluorescein and 1% lissamine green in 50 patients with dry eye (12 patients with Sjögren syndrome and 38 patients with non-Sjögren syndrome). Ocular surface disease index (OSDI), tear breakup time (BUT), and Schirmer test were evaluated. Digital photographs were taken after vital staining on the ocular surface, and the grade of staining in various areas was assessed. Correlation among the degrees of staining, OSDI, and ocular surface parameters was analyzed. RESULTS: The nasal conjunctiva evidenced greater staining compared with the temporal conjunctiva and cornea (P = 0.04). Staining of the nasal conjunctiva showed significant correlation with OSDI (P < 0.01) and BUT (P = 0.03). Staining of the temporal conjunctiva correlated significantly with OSDI (P = 0.01), and staining of the cornea correlated with BUT (P = 0.02). CONCLUSIONS: Double vital staining with 1% fluorescein and 1% lissamine green correlates with symptoms and some ocular surface parameters in patients with dry eye and helps to identify ocular surface changes easily. It may be a useful method for the diagnosis of dry eye and the assessment of the therapeutic effect in patients with dry eye syndrome.

Comparison of scanning laser polarimetry and optical coherence tomography in preperimetric glaucoma.

PURPOSE: This study was performed to compare the effectiveness of scanning laser polarimetry with variable corneal compensation (GDx VCC) and optical coherence tomography (Stratus OCT) for the detection of loss of the retinal nerve fiber layer (RNFL) in preperimetric glaucomatous eyes. METHODS: Sixty subjects with preperimetric glaucoma (60 eyes) and 60 normal subjects (60 eyes) were included. We measured the RNFL thickness with GDx VCC and Stratus OCT and analyzed the results by 12 clock hour RNFL measurements. The area under the receiver-operating characteristic curve was calculated, and the data from all clock hour segments were compared using regression analyses. RESULTS: The mean RNFL thickness for GDx VCC were 49.00 ± 17.23 µm and 59.4 ± 8.38 µm (p < 0.01), and for Stratus OCT, they were 86.43 ± 20.49 µm and 106.61 ± 9.57 µm (p < 0.01) in the patients with preperimetric glaucoma and normal group, respectively. The mean RNFL thickness for the clock hour evaluations were significantly different between the patients with preperimetric glaucoma and the normal group (p < 0.05). In preperimetric glaucoma, the area under the receiver-operating characteristic curve was the highest for the 12 clock hour RNFL thickness for GDx VCC (0.905) and the 7 clock hour RNFL thickness for Stratus OCT (0.903). GDx VCC and Stratus OCT RNFL measurements had significantly high correlations in the superior and inferior quadrants (r >0.750) and low correlation at the nasal quadrant (r = 0.210). CONCLUSIONS: Both GDx VCC and Stratus OCT instruments had similar correlations at each clock hour segment, and both were useful in the early detection of patients with preperimetric glaucoma.

Anomalous scleral insertion of superior oblique in Axenfeld-Rieger syndrome.

Axenfeld-Rieger syndrome (ARS) is associated with ocular and systemic anomalies. PITX2 is known to be a major controlling gene in the pathogenesis of ARS and is associated with differentiation in both the neural crest and mesoderm during eye development. A 4-year-old girl with bilateral ARS had 20 prism diopters (PD) of exotropia with 30PD of A- pattern deviation, more than 20PD of dissociated vertical deviation (DVD), and severe superior oblique overaction (SOOA). During surgery we observed that the SO inserted more posteriorly than normal. We believe this finding is one of the abnormal manifestations of the development of the extraocular muscles in ARS.