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Biomedical subjects

J M Rakic

Publications and source records attributed to J M Rakic.

15 recordsLinked to original sources

[Eye and ultraviolet light].

All the ocular structures, from cornea to retinal layer, can be damaged by exposure to the light radiations. Acute keratitis combined with conjunctivitis will result from an intensive photic exposure. On the other hand, pterygion more likely represents the consequence of chronic exposure to the ultraviolet rays. Exposure to the ultraviolet rays has been involved in the appearance of the typical yellow pigments of the nuclear cataract. Indeed, the physiopathological mechanisms are now progressively better understood. The progression of retinal degenerations might be influenced by uncontrolled exposure to ultraviolet rays, particularly during childhood. It is therefore useful to protect the eyes against ultraviolet sunrays. Filtering glasses seem to be one of the most effective ways to reach that objective.

Environmental Exposure↗

[Low dose intravitreal triamcinolone acetonide in the treatment of neovasular glaucoma].

PURPOSE: To report the effect of an intravitreal injection of 4 mg of crystalline triamcinolone acetonide (Kenacort) as symptomatic treatment of neovascular glaucoma. MATERIAL AND METHODS: This clinical study is based on clinical and experimental investigations that examined the tolerability and the angiostatic effect of triamcinolone acetonide. The study includes prospectively 8 eyes of 8 patients with neovascular glaucoma secondary to ischemic central retinal vein occlusion (n=8). All patients received an intravitreal injection of 4 mg of crystalline triamcinolone acetonide (0.1 cc) as the only procedure or in combination with transscleral cyclodiode as glaucoma treatment. Their mean age was 74.5 +/- 14.4 years. Mean intraocular pressure (IOP) was 38.9 +/- 9.3 mmHg. Mean follow-up was 6 months. RESULTS: 4 of 8 patients were treated by crystalline triamcinolone acetonide as the only procedure (n=3). Twenty seven days after intravitreal kenacort injection, the others four patients have been treated by transscleral cyclodiode (n=4) as glaucoma treatment. After injection, including the first postoperative day, patients report a subjective reduction of ocular pain. Furthermore no intra- or extraocular inflammatory reactions were observed during the follow-up. Intraocular pressure was significantly reduced to 18 +/- 6.2 mm Hg at the end of the follow-up period. When considering only the four patients in which the intraocular cortisone injection was the only procedure performed, mean intraocular pressure decreased from 41.75 +/- 7.05 mm Hg to 20.5 +/- 6.6 mm Hg. Iris neovascularisation was significantly decreased from grade IV to grade I in all patients at the end of the follow-up CONCLUSION: Intravitreal injection of 4 mg triamcinolone acetonide contributes to a better management of the neovascular glaucoma.

Aged↗

[Patient access to the medical file].

A new law regulates the access of the patients to their medical files in Belgium. The authors discuss the implications of this law for everyday medical practice.

Belgium↗

Role of plasminogen activator-plasmin system in tumor angiogenesis.

New blood formation or angiogenesis has become a key target in therapeutic strategies aimed at inhibiting tumor growth and other diseases associated with neovascularization. Angiogenesis is associated with important extracellular remodeling involving different proteolytic systems among which the plasminogen system plays an essential role. It belongs to the large serine proteinase family and can act directly or indirectly by activating matrix metalloproteinases or by liberating growth factors and cytokines sequestered within the extracellular matrix. Migration of endothelial cells is associated with significant upregulation of proteolysis and, conversely, immunoneutralization or chemical inhibition of the system reduces angiogenesis in vitro. On the other hand, genetically altered mice developed normally without overt vascular anomalies indicating the possibility of compensation by other proteases in vivo. Nevertheless, they have in some experimental settings revealed unanticipated roles for previously characterized proteinases or their inhibitors. In this review, the complex mechanisms of action of the serine proteases in pathological angiogenesis are summarized alongside possible therapeutic applications.

Animals↗

[Treatment of Graves macular edema with intravitreal injection of corticosteroids].

PURPOSE: To determine if intravitreal injection of triamcinolone is an effective option in treating severe macular oedema unresponsive to other treatments. METHODS: Fifteen eyes with severe macular oedema of long duration (9-30 months) were offered intravitreal injection of 4 mg triamcinolone. The visual acuity and anatomic responses were monitored with pre- and postoperative fluorescein angiography and optical coherence tomography (OCT). RESULTS: The minimal follow-up was 3 months (mean = 6 months). The central macular thickness evaluated by OCT decreased by 50%. This beneficial effect was correlated with a significant improvement in visual acuity. Ten of 15 patients (66%) improved their visual acuity by more than two Snellen lines. We could observe a significant increase in intraocular pressure (mean = 15%) due to corticosteroid medication. No injection-related complication occurred. One patient had to be retreated after 3 months due to recurrence of macular oedema. CONCLUSIONS: Intravitreal triamcinolone is a promising therapeutic option for severe macular oedema. Further study is warranted to evaluate the long-term efficacy and safety, as well as the need for retreatment.

Adult↗

Influence of plasminogen activator inhibitor type 1 on choroidal neovascularization.

High levels of the plasminogen activators, but also their inhibitor, plasminogen activator inhibitor 1 (PAI-1), have been documented in neovascularization of severe ocular pathologies such as diabetic retinopathy or age-related macular degeneration (AMD). AMD is the primary cause of irreversible photoreceptors loss, and current therapies are limited. PAI-1 has recently been shown to be essential for tumoral angiogenesis. We report here that deficient PAI-1 expression in mice prevented the development of subretinal choroidal angiogenesis induced by laser photocoagulation. When systemic and local PAI-1 expression was achieved by intravenous injection of a replication-defective adenoviral vector expressing human PAI-1 cDNA, the wild-type pattern of choroidal angiogenesis was restored. These observations demonstrate the proangiogenic activity of PAI-1 not only in tumoral models, but also in choroidal experimental neovascularization sharing similarities with human AMD. They identify therefore PAI-1 as a potential target for therapeutic ocular anti-angiogenic strategies.

Adenoviridae↗

Presence of oestrogen receptor type beta in human retina.

BACKGROUND/AIMS: Recent studies have demonstrated the existence of two oestrogen receptor subtypes alpha (ORalpha) and beta (ORbeta) with significant differences of expression among organs. Since important pathologies of human eye could be linked to hormonal status, the expression of ORbeta in ocular posterior segment was sought. METHODS: Immunohistochemical localisation of ORbeta and ORalpha protein and detection of OR mRNAs by reverse transcription-polymerase chain reaction (RT-PCR) were performed in macular and extramacular regions of the retina and in the choroid on male and female donors eyes. RESULTS: ORbeta protein was localised in the ganglion cell layer and in the choroid. At the transcriptional level, mRNA for ORbeta and for ORalpha were both present. Local differences in the expression level were observed, however, suggesting the possibility of variation in the ratio of ORalpha v ORbeta. CONCLUSIONS: The coexistence of two oestrogen receptor subtypes in the human ocular posterior segment raises acute questions about their potential physiological role, but offers a perspective for preferential targeting of a specific receptor subtype.

Aged↗

Lens epithelial cell proliferation in human posterior capsule opacification specimens.

In previous in vitro studies on capsular bags it was shown that, after a sham extracapsular cataract extraction (ECCE) on human donor eyes, lens epithelial cells (LECs) show, in the short term, a dramatically elevated mitotic activity as compared to that in the intact lens. The long term in vivo proliferation of LECs in human lenses after ECCE and intraocular lens (IOL) implantation has not been studied until now. In the present study, the mitotic activity of LECs in human post-mortem eyes with posterior capsule opacification (PCO) was investigated. Human lenses with signs of PCO were dissected from donor eyes and incubated in MEM, supplemented with fetal calf serum, for 1 day (n = 10) or 7 days (n = 9). Six additional specimens were cultured for 7 days after removal of the IOL and lens fibres. After the incubation period, mitotic activity was estimated using the BrdU procedure and the Ki67 proliferating cell marker. The mean number of BrdU-positive nuclei in the intact PCO specimens was at a level of 7.5 (day 1) and 6.5 (day 7). Removal of the IOL and the lens fibres leads to a ten-fold increase in BrdU positive cells (mean = 84.5). No correlation with donor age was found. The Ki67 observations corroborate the BrdU results. The results demonstrate that after an initial rise in proliferative activity, as shown in the capsular bag model, the mitotic activity of LECs returns to a rate comparable to that in intact cultured non-cataractous lenses. As in control lenses, removal of lens fibres significantly elevated the proliferative activity of the remaining LECs. Suppression by newly formed differentiated lens fibres in the in vivo capsular bag may be responsible for this return to control levels of mitotic activity of LECs in the PCO specimens.

Aged↗

Lens cell populations studied in human donor capsular bags with implanted intraocular lenses.

PURPOSE: Posterior capsule opacification is an ongoing cellular redistribution process. The level of viable cell coverage was therefore determined in human donor capsular bags with implanted intraocular lenses, and cellular morphology and ultrastructure were investigated in relation to cell type and level of differentiation. METHODS: Donor capsular bags, retrieved at intervals of 4 months to 13 years after surgery, were investigated by phase optics before fixation. Postfixation techniques included scanning electron microscopy and transmission electron microscopy of sections and immunofluorescent staining of cytoskeletal proteins in wholemounts. RESULTS: All the capsular bags contained a large population of viable cells on the capsular surfaces. Cells on the anterior face of the anterior capsule and in the spaces around the intraocular lens had an elongated morphology and expressed alpha-smooth muscle actin. The cells formed light-scattering, multilayered aggregates and strands that were surrounded by layers of extracellular matrix. The regions between the intraocular lens and the equator of the bags were populated by monolayers of epithelial cells of normal morphology and ultrastructure, on both the anterior and posterior capsules. In some regions the apical surfaces of the two epithelial monolayers were in contact, and in some parts of the equatorial regions, differentiation of cells into well-organized fiberlike cells was evident. CONCLUSIONS: Human capsular bags contain a large population of viable cells for many years after cataract surgery. Cells in the regions around the intraocular lens undergo transition to a mesenchymal type. Cells peripheral to these regions can form a stable closed microenvironment in which both normal epithelial morphology and differentiation to fiberlike cells are maintained.

Actins↗

Separation of fibres from the capsule enhances mitotic activity of human lens epithelium.

Proliferation and migration of lens epithelial cells is at the origin of after-cataract, currently the main side effect of cataract surgery. Extracapsular cataract surgery necessitates opening of the anterior lens capsule and removal of the lens fibres before an intraocular lens can be placed in the cleaned capsular bag. The present study was aimed at testing the potential of the lens capsule and the fibres to affect the mitotic activity of the lens epithelial cells in human donor eyes. Pairs of human lenses used in this study were subjected to two different experimental conditions. In the first, only a small anterior capsulorhexis was made. In the other, fibres were separated from the epithelium by gentle hydrodissection, the nucleus was rotated and, either left in the capsular bag or removed by hydroexpression. The specimens were cultured for 48 hr in MEM with 2% serum. Mitotic activity was assessed by immunohistochemistry using the bromodeoxyuridine (BrdU) incorporation technique. Fellow lenses of the same donors were cultured intact as controls. Anterior capsulorhexis showed a small but significant (P < 0.02) increase in the number of BrdU positive nuclei in the equatorial region but not in the wound area. Lenses where fibres were separated from the epithelium showed a large increase in BrdU incorporation in the germinative region, as compared to the intact control lenses (P < 0.01). BrdU incorporation was highest when fibres were removed. Lens capsule integrity and the presence of contacts between fibres and epithelial cells may have a role in the control of the mitotic activity of the lens epithelium. The data recorded here could be useful for understanding lens cell biology and prevention of after-cataract.

Adolescent↗

Complicated posterior capsulorhexis: aetiology, management, and outcome.

BACKGROUND: A 1 year retrospective analysis of 650 patients, who underwent a posterior capsulorhexis on their intact capsules, was performed to examine the incidence of complications, their aetiologies, and the outcome. METHODS: Data were analysed on 32 patients with complicated capsulorhexis for type of surgery, preoperative and postoperative factors, and relative risk factors for vitreous issue. RESULTS: There were six patients with vitreous loss. The posterior capsulorhexis was uncontrolled in 14 cases and difficult to perform in 12 cases. Implantation into the capsular bag was possible in all cases. Systemic vascular hazard and old age (over 80 years) were found to be statistically significant risk factors for vitreous loss (p = 0.002 and p = 0.03 respectively). The mean follow up was 13.5 months (range 4-25 months). One patient developed a retinal detachment and two had a transient clinical cystoid macular oedema. Visual acuity of > or = 20/40 was obtained in 93% of the patients. CONCLUSION: Loss of control of the posterior capsulorhexis has a low incidence but can lead to serious problems during surgery. A good knowledge of the technique is necessary to complete the procedure with a posterior capsulorhexis of the optimum size without vitreous loss.

Adult↗

Human lens epithelial cell proliferation in a protein-free medium.

PURPOSE: The ocular humors are relatively low in protein, yet cell growth in the human capsular bag still occurs after extracapsular cataract extraction (ECCE) surgery. This resilient growth gives rise to posterior capsule opacification (PCO) in a significant proportion (30%) of patients. This study compared the ability of human lens cells to proliferate in serum-supplemented and protein-free medium. METHODS: Sham cataract operations were performed on human donor eyes. The capsular bag was dissected free, pinned flat on a petri dish, and incubated in Eagle's minimal essential medium (EMEM) alone or in EMEM supplemented with 10% fetal calf serum. Observations were made by phase-contrast microscopy. At the endpoint, capsules were studied by fluorescence or electron microscopy. Mitotic activity was identified using Bromo-2-deoxyuridine labeling and detection techniques. When required, an intraocular lens was implanted when surgery was performed. RESULTS: It was found that human lens cells from a wide age spectrum of donors proliferate and migrate on the lens capsule in the absence of added protein. The rate of growth was age-dependent, such that the posterior capsule was completely confluent after 8.0 +/- 0 days (n = 3) and 24.4 +/- 5.3 days (n = 3) for donor lenses aged < 40 years and > 60 years, respectively. The outgrowth of epithelial cells gave rise to capsular contraction, wrinkling, and increased light scatter. Growth on the anterior surface of the intraocular lens was less prolific than on the posterior capsule. CONCLUSION: The protein-free model replicates many features of clinically-observed PCO. The resilient cell growth on the natural collagen capsule explains the high prevalence of PCO, especially in younger patients, and suggests that inflammation and external growth factors are not necessary for PCO. Furthermore, the protein-free capsular bag system can be used to explore fundamental questions concerning the autocrine control of lens epithelial cell survival and growth.

Adult↗

[Cyclosporin in ophthalmology].

Cyclosporine A is a selective T-cell immunosuppressant, and doesn't inhibit the phagocytic system to the same degree as do steroids. Significant nephrotoxicity has been associated with its systemic use for solid organ transplantation or chronic idiopathic uveitis. Topical administration of CsA 2% in olive oil reduces the risk of systemic side-effects and appears to be well tolerated without local toxicity. Ocular penetration currently limits its indications for corneo-scleral immune diseases or high-risk corneal grafts.

Administration, Topical↗

[Diabetic retinopathy].

Diabetic retinopathy remains a serious cause of blindness in the Western World. Its major clinical signs and management are reviewed, with particular focus on advances in the diagnosis and treatment of diabetic macular edema.

Blindness↗