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N H Chong

Publications and source records attributed to N H Chong.

17 recordsLinked to original sources

Measurement of TIMP-3 expression and Bruch's membrane thickness in human macula.

An increase or accumulation in tissue inhibitor of matrix metalloproteinases-3 (TIMP-3) protein in Bruch's membrane with ageing in normal eyes, and in age related macular degeneration (AMD) has been previously demonstrated. The purpose of this study was to determine whether the expression of TIMP-3 mRNA increases with age, and to define any relationship between altered expression and Bruch's membrane thickness. Normal eyes were obtained from 30 donors (age range 15-90 years). Full-thickness 8 mm macular punches centred on the fovea were taken to allow removal of the chorioretinal complex, for subsequent nucleic acid extraction. Samples were normalized for RNA degradation using beta-actin reverse transcriptase-polymerase chain reaction (RT-PCR). A competitive RT-PCR was then used to allow measurement of TIMP-3 gene expression in each sample. The tissue adjacent to that used for nucleic acid extraction was processed histologically to allow determination of Bruch's membrane thickness. Bruch's membrane thickness was found to increase with age (P < 0.01), but TIMP-3 expression, as measured by competitive RT-PCR, was not significantly increased with age (P = 0.19). An inverse correlation was noted between TIMP-3 expression and Bruch's membrane thickness after controlling for age (P = 0.032). The results of this study suggest that TIMP-3 expression does not alter significantly with age. Therefore, accumulation of the TIMP-3 protein must occur by a mechanism other than increased expression. TIMP-3 protein levels may still prove to contribute to events associated with ageing in the macula, such as matrix remodelling in Bruch's membrane. Further studies are required to elucidate the precise interactions and turnover of the TIMP-3 protein, and resulting changes in the control of matrix metalloproteinase activity in the ageing macula.

Adolescent↗

TIMP-3, collagen, and elastin immunohistochemistry and histopathology of Sorsby's fundus dystrophy.

PURPOSE: Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP-3) gene have previously been identified in patients with Sorsby's fundus dystrophy (SFD). We evaluated the ocular distribution of TIMP-3 and other extracellular constituents in SFD. METHODS: The eyes of an SFD donor with a confirmed TIMP-3 mutation were examined using histologic techniques demonstrating connective tissue, calcium, and lipid. Immunohistochemical analyses were performed using antibodies against TIMP-3, collagen type IV, V, and VI, laminin, fibronectin, elastin, and fibrillin. Electron microscopy also was used. RESULTS: A subretinal pigment epithelium (sub-RPE) deposit similar to that previously described was seen. A morphologically similar but different deposit was present internal to the nonpigmented ciliary epithelium (NPCE). Both deposits contained collagens, elastin, glycosaminoglycans, lipids, and calcium. Immunolabeling of TIMP-3 was found in the basement membrane of the NPCE, Bruch's membrane, and choroidal vessels in normal control subjects. In SFD, immunolabeling of TIMP-3 also was present in the sub-RPE deposit and in the inner portion of the ciliary body deposit. TIMP-3 immunoreactivity was more extensive in the SFD eye. The pattern of elastin immunoreactivity was remarkably similar to that of TIMP-3. Electron microscopy revealed a morphologically altered elastic layer of the Bruch's membrane. CONCLUSIONS: Sub-RPE TIMP-3 immunoreactivity appears more extensive in SFD than in control subjects. There is also a correspondence between TIMP-3 and elastin immunoreactivies, which invites speculation as to a link between the SFD TIMP-3 mutation and altered elastin processing. The accumulation of abnormal material in SFD is more widespread than previously reported. In view of this, SFD might be better termed Sorsby's ocular epitheliopathy.

Aged↗

An immunohistochemical study of an autosomal dominant feline rod/cone dysplasia (Rdy cats).

An autosomal dominant, early onset feline model of rod/cone dysplasia has been described. The clinical features, light and electron microscopy, and the electrophysiology were documented. We have now examined in more detail the histopathological and immunohistochemical changes during the early phase of the disease using antibodies against opsin, synaptophysin, glial fibrillary acidic protein (GFAP) and an epithelial marker (MNF118). We have also demonstrated programmed cell death by a modified TUNEL (Terminal deoxynucleotidyl transferase, Uridine triphosphate, Nick End Labelling) technique. In the Rdy cats, there was significant photoreceptor degeneration between 5 and 17 weeks of age. The TUNEL-labeled cell and pyknotic cell counts in the outer nuclear layer peaked at around 9 weeks of age. Accumulation of opsin in the entire outer nuclear layer of the retina was noted with opsin-immunolabeled rod neurite sprouting. There was a reduction in synaptophysin immunoreactivity in the outer plexiform layer. The Muller cells were activated and expressed GFAP. No significant change of immunolabeling of MNF118 was found. These findings closely parallel those seen in human RP.

Animals↗

Repeated injections of a ciliary neurotrophic factor analogue leading to long-term photoreceptor survival in hereditary retinal degeneration.

PURPOSE: To determine whether ciliary neurotrophic factor (CNTF) or brain-derived neurotrophic factor (BDNF) treatment leads to long-term photoreceptor survival in hereditary retinal degeneration. METHODS: An autosomal dominant feline model of rod-cone dystrophy was used throughout the study with two normal animals. In the first experiment, intravitreal injections of a human CNTF analogue (Axokine; Regeneron Pharmaceuticals, Tarrytown, NY) were administered to one eye of each animal (n = 10) beginning on postnatal day 10 and were repeated every 4 weeks. Clinical and histopathologic examinations were performed at 5.5, 9.5, and 13.5 weeks. In the second experiment, animals (n = 17) were randomly assigned to receive intravitreal injections of either Axokine (at half the initial dose), human BDNF, or the vehicle for Axokine to one eye at 5.5 weeks. The same therapy was repeated every 4 weeks in each group. Clinical and histopathologic examinations were performed at 9.5, 13.5, and 17.5 weeks. Photoreceptor survival was assessed by cell counting. Apoptotic cells were identified by morphology and a modified TdT-dUTP terminal nick-end labeling (TUNEL) technique. In the third experiment, two normal animals were treated with Axokine as in the first experiment. Glial fibrillary acidic protein ((GFAP) immunohistochemistry was performed to assess glial cell reaction. RESULTS: In the first two experiments, Axokine significantly prolonged photoreceptor survival (P < 0.01) and reduced the presence of apoptotic cells (P < 0.05) and TUNEL-positive cells (P < 0.05). In the second experiment, results in the the BDNF- and sham-injected eyes were not significantly different from those in the untreated eyes. Minimal posterior subcapsular cataract and mild retinal folds were found in all Axokine-treated eyes in both dystrophic and normal animals. These complications were milder in the second experiment when injections were started later and at a reduced dose. GFAP immunolabeling was also increased in all Axokine-treated eyes. CONCLUSIONS: Axokine, but not BDNF, delays photoreceptor loss in this hereditary retinal degeneration. Repeated injections maintain the protective effect.

Animals↗

Photoreceptor rescue.

Photoreceptor cell death is the final, irreversible event in many blinding diseases including retinitis pigmentosa, age-related macular disease and retinal detachment. This paper examines the potential strategies for preventing photoreceptor cell death in the context of current understanding of the mechanisms of cell death. There is evidence to suggest that photoreceptor cells are inherently vulnerable, apoptosis is the final common pathway of photoreceptor cell loss, and other retinal cells play an important role in the survival of rods and cones. Furthermore, the rationale of using neurotrophic factors as therapeutic agents in retinal degeneration is discussed in detail. Photoreceptor rescue by manipulation of genes involved in apoptosis and some pharmacological agents is also described.

Animals↗

Long-term results of combined cataract and glaucoma surgery versus trabeculectomy alone in low-risk patients.

PURPOSE: To compare the long-term results of combined extracapsular cataract extraction (ECCE), intraocular lens (IOL) implantation, and trabeculectomy with those of trabeculectomy alone in low-risk patients. SETTING: An ophthalmic department in a British general district hospital. METHODS: We did a retrospective analysis of the case records of all low-risk patients who had either combined ECCE, IOL implantation, and trabeculectomy (combined group) or trabeculectomy alone between August 1991 and February 1993 with a minimum of 12 months follow-up (mean 21 months). The combined group comprised 21 patients (14 women) and the trabeculectomy group, 24 patients (18 women). The mean ages were 79.8 years (range 66 to 90 years) and 76.0 years (range 61 to 87 years), respectively. We measured final intraocular pressure (IOP), number of medications used, best corrected visual acuity, visual field, and complication rates. RESULTS: Average IOPs at diagnosis, the preoperative visit, and last follow-up visit were 27.6, 23.1, and 15.6 mm Hg, respectively, in the combined group and 31.8, 26.7, and 15.3 mm Hg, respectively, in the trabeculectomy group. The differences between groups were not statistically significant at any stage. All patients had an IOP lower than 22 mm Hg at the last follow-up. In more than 75% of patients in the combined group, visual acuity improved by more than one Snellen line. CONCLUSIONS: The combined procedure compared favorably with trabeculectomy alone in low-risk patients.

Aged↗

Fibrinogen, cholesterol and smoking as risk factors for non-arteritic anterior ischaemic optic neuropathy.

Non-arteritic anterior ischaemic optic neuropathy (AION) is thought to be due to occlusion of the posterior ciliary circulation. Raised lipid and fibrinogen concentrations are recognised risk factors for vessel occlusion in cardiovascular disease and stroke but, although suspected as risk factors in non-arteritic AION, they have not been studied in this condition. We therefore performed a case-control study on 41 patients with non-arteritic AION, looking at these and other atherosclerotic risk factors. The odds ratio of cholesterol being > 6.5 mmol/l in non-arteritic AION was 2.7 (95% confidence interval 1.09 to 6.65; p < 0.05) and of fibrinogen being > 3.6 g/l was 5 (2.66 to 9.39; p < 0.05). Smoking was also found to be significantly associated with non-arteritic AION, the odds ratio being 16 (3.23 to 79.23; p < 0.001). These were the only risk factors found to be significantly associated with non-arteritic AION. This raises the possibility that appropriate medical management of these factors could be given to prevent recurrence in the fellow eye.

Aged↗

Is measuring intraocular pressure necessary on the first post-operative day following uncomplicated cataract surgery?

A prospective study was undertaken to assess whether the level of intraocular pressure (IOP) on the first day after cataract surgery could be estimated by clinical examination only, thereby removing the need for applanation tonometry. A total of 70 patients underwent uncomplicated extracapsular cataract extraction and intraocular lens implantation. The following day a Consultant, Registrar and Senior House Officer were asked to identify those patients with significantly raised IOP (> 27 mmHg) using slit lamp examination only. A fourth examiner, masked to the assessments of the three observers, measured the IOP using the Goldmann applanation tonometer. Pressures of > 27 mmHg by Goldmann tonometry were found in 10 patients (14%) of which 8 (80%) were missed by all three ophthalmologists. Formal measurement of IOP appears a necessary part of the post-operative assessment after uncomplicated cataract surgery.

Aged↗

Visual acuity and pupillary reactions after peribulbar anaesthesia.

The effect of peribulbar anaesthesia on optic nerve function in 20 patients, before and after cataract surgery, was measured. All the patients had decreased visual acuity. Five (25%) had no perception of light. Seventeen (85%) developed a relative afferent pupil defect (RAPD). No patients saw the operating instruments. Seven (35%) had improved visual acuity immediately postoperatively. Patients should be warned that they may lose vision completely on being given a peribulbar anaesthetic; however their vision will improve, but not necessarily immediately, postoperatively. Examination for an RAPD is a good method of providing reassurance that the operating instruments will not be seen.

Aged↗

Extensive visual loss with topical facial steroids.

Steroid creams applied topically to the skin are routinely used in the treatment of many dermatoses. Their use on the face in severe atopic eczema is relatively common. We report a series of three patients who whilst using topical facial steroids developed advanced glaucoma. A further two cases of ocular hypertension secondary to topical facial steroids are also described. This is the first series of cases to be reported demonstrating the potentially blinding complications of topical facial steroids. Recommendations are made with regard to screening such patients for glaucoma.

Administration, Topical↗

Is ophthalmic therapy often overlooked in hospital wards?

In a prospective study regarding the accuracy of ophthalmic drugs prescriptions of 55 inpatients in two general teaching hospitals, it was found that: only 27.3% of these patients had their ocular therapy correctly prescribed; 38.2% had their eye medications incorrectly prescribed; and 34.5% had no ophthalmic drugs prescribed. The authors conclude that more care during case history taking could prevent such errors.

Drug Prescriptions↗