Efficacy of laser peripheral iridoplasty and iridotomy on medically refractory patients with acute primary angle closure: a three year outcome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Argon laser peripheral iridoplasty (ALPI) is proved to be effective in lowering intraocular pressure (IOP) of patients with mild acute primary angle closure (APAC). It is unclear whether this laser treatment is equally efficient in managing patients with severe APAC. This study aimed to evaluate the IOP-lowering efficacy of ALPI and laser peripheral iridotomy (LPI) on patients with refractory APAC, who have previously responded poorly to intensive medical therapy.</p><p><b>METHODS</b>Thirty-six patients (8 men and 28 women) were identified as medically refractory APAC, who still had ocular pain, red eye, hazy cornea, closed anterior chamber (AC) angle, and IOP of not less than 21 mmHg after two days or more of anti-glaucoma medication. All enrolled patients underwent ophthalmologic examinations including measurement of visual acuity (VA), best corrected VA (BCVA), IOP, biomicroscopy, and gonioscopy followed by ALPI immediately in the APAC eye and LPI in both eyes.</p><p><b>RESULTS</b>All patients were affected unilaterally, with average age of (54.6 ± 11.7) (range, 37.0 - 75.0) years old. The mean IOP value of the affected eyes dropped from (31.6 ± 7.7) (range, 21.0 - 39.0) mmHg at enrollment to (18.4 ± 8.7) (range, 10.0 - 27.0) mmHg 2 hours after ALPI. At follow-up day 7, the mean IOP value maintained at (14.8 ± 4.2) (range, 9.0 - 21.0) mmHg, which was significantly different (P = 0.000) compared with baseline. The average decrease of IOP in the APAC eyes was (16.8 ± 7.4) (range, 12.0 - 21.0) mmHg. At follow-up three years later, the mean IOP of the APAC eyes stabilized at (16.3 ± 3.2) (range, 9.0 - 20.0) mmHg with at least 180° of AC angle opened.</p><p><b>CONCLUSION</b>ALPI and LPI lower the IOP of medically refractory cases of APAC though they have responded poorly to anti-glaucoma medication.</p>

Axonal loss and blood flow disturbances in the natural course of indirect traumatic optic neuropathy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Indirect traumatic optic neuropathy (TON) is an acute injury of the optic nerve associated with severe visual dysfunction, which may be a result of secondary mechanical injury and vascular disorder of the optic nerve due to trauma. We analyzed the natural course of axonal loss and blood flow disturbances in patients with indirect TON to find a possible therapeutic window.</p><p><b>METHODS</b>A cohort of 54 patients with indirect TON recruited between October 2008 and October 2010 at Beijing Tongren Hospital was retrospectively analyzed. The patients were divided into no light perception group (NLP) and better than NLP (btNLP) group. Specifically, the thickness of the retinal nerve fiber layer (RNFL) measured by spectral domain optical coherence tomography (SD-OCT), and hemodynamic parameters of the ophthalmic artery (OA), central retinal artery (CRA) and posterior ciliary artery (PCA) were determined.</p><p><b>RESULTS</b>Two weeks after injury, there was a statistically significant decrease in the thickness of RNFL in the btNLP group as compared with the fellow control eyes (P < 0.05). In contrast, in the NLP group, RNFL thickness slightly increased for 2 weeks following injury, then overtly reduced after 4 weeks (P < 0.05). Peak systolic velocity (PSV) of CRA was significantly decreased 4 weeks after injury (P < 0.05) in both the NLP group and btNLP group (P < 0.05). The thickness of RNFL in the NLP group was negatively correlated with PSV of CRA after 1 week of injury (P < 0.05, r = -0.962).</p><p><b>CONCLUSIONS</b>SD-OCT is a useful supplement in detecting the axonal loss in TON. The dynamic change of the thickness of RNFL appears to correlate with the hemodynamic disturbances in the natural course of TON. The first 2 weeks following an injury is critical and should be considered as the therapeutic window for TON patients.</p>

Enhanced expression of proneurotrophins in elevated introcular pressure-induced rat retinal ischemia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Proneurotrophins such as the precursor of nerve growth factor (proNGF) and the precursor of brain-derived neurotrophic factor (proBDNF) interacted with sortilin and p75(NTR) to form a complex capable of activating an apoptotic signaling. We found that the expression of p75(NTR) and sortilin was increased in ischemic retina induced by elevated intraocular pressure (IOP), but the protein expression changes of proNGF and proBDNF in the same situation were not clear. This study aimed to ascertain the protein expression changes of proNGF and proBDNF in ischemic retina induced by elevated IOP.</p><p><b>METHODS</b>Expression of proBDNF and proNGF was examined by double-labeling immunochemistry in normal rat retina, examined using Western blotting and analyzed using statistical methods in ischemic retina induced by elevated IOP.</p><p><b>RESULTS</b>Immunocytochemistry showed that the proBDNF expressed in the ganglion cell layer (GCL) while the proNGF primarily existed in both the nerve fiber layers (NFL) and large ganglion cell bodies of normal rat retina. Western blotting analysis demonstrated that the molecule weights of 28 kD (proBDNF)/25 kD (proNGF) band were increased significantly (P < 0.05) at days 3, 5 and 7 after retinal elevated-IOP-induced ischemia.</p><p><b>CONCLUSION</b>ProBDNF expressed in the GCL and proNGF primarily presented in NFL and large ganglion cell bodies of normal rat retina, the protein expression forms of 28 kD proBDNF and 25 kD proNGF increased in ischemic retina induced by elevated IOP.</p>

Clone and expression of human cytomegalovirus UL144 gene and its effects on dendritic cells / 第二军医大学学报

Objective: To construct a recombinant adenovirus vector carrying human cytomegalovirus (hCMV) UL144 gene and to explore the biological characteristics of UL144 gene-modified DCs. Methods: The UL144 gene was amplified from hCMV DNA, which was extracted from hCMV-DNA positive serum. The recombinant adenovirus vector carrying hCMV UL144 gene was constructed with AdEasy system and then transfected into HEK293 cells to create recombinant adenovirus Ad-UL144. The expression of inserted gene was identified by RT-PCR. The recombinant adenovirus was then transfected into mice myeloid dendritic cells. The surface proteins of dendritic cells were analyzed by FACS, and cytokines in supernatant were detected by ELISA. T cell proliferation stimulated by gene-modified DC was examined by 3H-TdR uptake assay. Results: The UL144 gene was successfully cloned into the pAdEasy-1 plasmid. The recombinant adenovirus Ad-UL144 was packed in HEK293 cells, with a viral titer of 3×10 10 pfu/ml. DCs infected with AdCMV-UL144 had markedly decreased surface expression of CD80, CD86 and I-Ad (P < 0.01). The contents of TNF-α, IL-6 and IL-1β were significantly decreased in the supernatant of AdCMV-UL144 modified DCs (P < 0.05). T cell proliferation ability induced by gene-modified DC was obviously lower than in the DC control group (P < 0.01). Conclusion: UL144-modified DCs can maintain a relative immature status, and have reduced stimulating activity upon the proliferation and activation of T cells in vitro.

Time course degeneration and expression of glial fibrillary acidic protein in mer-knockout mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Müller cells in the mammalian retina normally express low levels of glial fibrillary acidic protein (GFAP); however, its expression is upregulated in response to the loss of retinal neurons. The change in expression of GFAP is one of the earliest indicators of retinal damage and is correlated with the time course of disease. The aim of this study was to investigate the time course of degeneration and the expression of GFAP in the retina of mer knockout mice.</p><p><b>METHODS</b>A total of 30 mer knockout mice, aged from 15 - 20 days to 1 year and 32 age-matched wild type mice as controls were tested. Immunohistochemistry was used to show the expression of GFAP in the central and peripheral retina of mer knockout and control mice at postnatal age of 15 days (P15d), 20 days (P20d), 4 weeks (P4w), 6 weeks (P6w), 8 weeks (P8w), 3 months (P3m), 6 months (P6m) and 1 years (P1y).</p><p><b>RESULTS</b>The expression of GFAP in the central and peripheral retina of wild type mice was limited to the retinal ganglion cell and nerve fiber layers. In the central retina of mer knockout mice, GFAP expression was upregulated at P4w and GFAP immunolabelling penetrates across the entire thickness of the retina at P8w; whereas in the peripheral retina, the GFAP expression was upregulated at P20d and GFAP immunolabelling penetrates the entire retina after P4w.</p><p><b>CONCLUSIONS</b>Increased expression of GFAP in Müller cells of mer knockout mice occur at P20d in the peripheral retina and P4w in the central retina. GFAP expression in Müller cells appears to be a secondary response to the loss of retinal neurons. Increased expression of GFAP may occur prior to any detectable morphological changes in the retina. This study suggests that the loss of retinal neurons may begin in the early stages of retinitis pigmentosa, prior to the discovery of any morphological changes in the retina.</p>

Loss of melanopsin-containing retinal ganglion cells in a rat glaucoma model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Glaucoma can cause progressive damage to retinal ganglion cells. These cells can be classified as cells projecting to the superior colliculus and melanopsin-containing retinal ganglion cells, which project to the suprachiasmatic nucleus. This study was to investigate the effects of chronic intraocular pressure elevation on melanopsin-containing retinal ganglion cells in rats.</p><p><b>METHODS</b>Chronic intraocular pressure elevation was induced in one eye of adult Wistar rats by cauterization of three episcleral veins. Intraocular pressure was measured at different intervals with a rebound tonometer. Superior collicular retinal ganglion cells were retrogradely labeled from the superior colliculus with Fluorogold. Melanopsin-containing retinal ganglion cells were visualized by free-floating immunohistochemistry on whole-mount retinas. The number of labeled superior collicular and melanopsin-containing retinal ganglion cells were counted in the sample areas on flat-mounted retinas.</p><p><b>RESULTS</b>Compared with contralateral control eyes, the numbers of both superior collicular and melanopsin-containing retinal ganglion cells were significantly reduced after 12 weeks of experimental intraocular pressure elevation ((2317.41 +/- 29.96)/mm(2) vs (1815.82 +/- 24.25)/mm(2); (26.20 +/- 2.10)/mm(2) vs (20.62 +/- 1.52)/mm(2), respectively). The extent of cell loss of the two types of retinal ganglion cells was similar. However, no morphologic changes were found in melanopsin-containing retinal ganglion cells.</p><p><b>CONCLUSION</b>Both melanopsin-containing and superior collicular retinal ganglion cells were damaged by chronic ocular hypertension, indicating that glaucomatous neural degeneration involves the non-image-forming visual pathway.</p>