Macular disease in related rhesus monkeys

During (January) 1986–(May) 1988, we examined 272 eyes in 136 rhesus monkeys in the closed Cayo Santiago colony of the Caribbean Primate Research Center of the University of Puerto Rico. Seventy-eight eyes were less than 10 years of age. One hundred and ninety-four were aged 10–28 years. The fundi were examined and photographed. Fluorescein angiography was performed in some eyes. Selected cases were evaluated for acuity loss by recording of pattern-evoked retinal and cortical signals. Light and electron microscopy were used to evaluate the pigment epithelium of some animals. Thirty-eight percent of all eyes had posterior pole drusen. Incidence was highly age-related. When late-stage lesions were found, we did not see neovascularization, but late hyperfluorescence was consistent with degenerative scarring and atrophy. Electrophysiology demonstrated moderately reduced acuity in the presence of numerous macular drusen. Electrooculograms were low normal. Histopathology showed changes identical to those reported in human age-related macular degeneration. No eyes less than 10 years of age had confluent drusen or disciform-like lesions. The incidence of drusen in samples of some social groups was much higher than others.     

兔腰椎间盘退变模型的建立及影像学分析

目的：建立腰椎间盘退变的动物模型并进行CR和MRI观察.方法：选用新西兰兔20只,沿右腹直肌外缘做15 cm长切口,钝性剥离腹膜至腰椎横突前外侧,咬除右侧L5、L6横突,显露上述节段椎间盘,斜形切开纤维环约1.5 mm,未伤及髓核,然后逐层缝合.所有动物在标准条件下饲养,分别于术后2、4、8、20、40周行腰椎计算机x线摄影术（CR）和核磁共振成像（MRI）以检测终板下骨及髓核的变化.结果：术后作为自体对照组的L1、2、L2、3椎间盘未见异常,而手术组L4、5、L5、6椎间盘则相继出现T2加权像低信号、腰椎不稳畸形,终板下骨质硬化,椎体边缘骨赘增生,椎间隙变窄,椎间盘后突和硬膜囊受压等改变.对手术节段及其邻近和完全正常节段椎间盘髓核信号值的定量分析显示,手术组椎间盘T2加权像信号值减低在术后4、8、20、40周与正常对照组对比具有统计学意义,而临近椎间盘L3、4、L6、7手术8周后与正常椎间盘对比有显著差异.CR扫描结果显示：手术节段椎间盘终板下信号值减低与对照组相比4周后就开始有显著差异.结论：应用纤维环切开法可获得可靠的新西兰大白兔椎间盘退变模型,可通过MRI及CR在早期加以证实.     

Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases

Unrelated patients with achromatopsia, macular degeneration with onset under age 50 years, cone degeneration or dysfunction, cone-rod degeneration, or macular malfunction were screened for mutations in the three genes known to be associated with achromatopsia: the GNAT2 gene encoding the alpha subunit of cone transducin and the CNGA3 and CNGB3 genes encoding the alpha and beta subunits of the cone cGMP-gated cation channel. We found no examples of patients with GNAT2 mutations. Out of 36 achromats, 12 (33%) had mutations in CNGA3 (13 different mutations including five novel mutations) and 12 (33%) had mutations in CNGB3 (six different mutations including four novel mutations). All achromats with CNG mutations had residual, presumably cone function as determined by computer-averaged 30-Hz electroretinograms (ERGs). There was considerable variability in acuity and color vision, with most patients having acuities of 20/200-20/400 and complete absence of color perception, and others having acuities of 20/25-20/40 and some color vision. Two pseudodominant achromatopsia cases were uncovered, both with CNGA3 mutations, including one family in which some compound heterozygotes with achromatopsia mutations were clinically unaffected. We found two novel CNGB3 changes in three patients with juvenile macular degeneration, a phenotype not previously associated with mutations in the cone channel subunits. These patients had subnormal acuity (20/30-20/60), normal to subnormal color vision, and normal to subnormal full-field cone ERG amplitudes. Our results indicate that some patients with channel protein mutations retain residual foveal cone function. Based on our findings, CNGB3 should be considered as a candidate gene to be evaluated in patients with forms of cone dysfunction, including macular degeneration.     

Effects of pinealectomy and exogenous melatonin on rat hearts

The effects of pinealectomy and administration of melatonin, the major secretory product of the pineal gland, which is a direct free radical scavenger and an indirect antioxidant, were studied in rat hearts on the basis of cardiac morphology and biochemical findings. Three groups of Wistar rats were used: one group was the sham-operated control, one group consisted of pinealectomized rats and one group consisted of pinealectomized rats that were treated with melatonin. Serum cholesterol, tissue levels of malondialdehyde (MDA) and reduced glutathione (GSH), and heart weight were determined. Histochemical staining with the Van Gieson, PAS/Alcian blue at pH 2.5 and Masson's trichrome methods were performed in addition to hematoxylin-eosin staining. Levels of serum cholesterol and tissue MDA, and heart weight were increased in pinealectomized rats whereas GSH levels did not change. Melatonin administration reversed these effects. Microscopically, myocardial fibrosis and myxomatous degeneration of cardiac valves were detected in all pinealectomized rats. It can be concluded that pinealectomy of rats causes morphological changes in rat hearts, and short-term application of melatonin does not reverse these changes.     

Genetic susceptibility to age related macular degeneration

Age related macular degeneration (AMD) is the leading cause of visual impairment in the elderly and a major cause of blindness in the developed world. The disease can take two forms, geographic atrophy and choroidal neovascularisation. The pathogenesis of AMD is poorly understood. There are undoubtedly environmental and other risk factors involved and the adverse effect of smoking is well established. Several studies have shown that genetic factors are important but leave uncertainty about the magnitude and nature of the genetic component and whether it varies with the type of AMD. Several hereditary retinal dystrophies show similarities to AMD and these genes are potential candidate susceptibility genes. Particular interest has focused on the ABCR gene which is responsible for autosomal recessive Stargardt macular dystrophy. It has been claimed that heterozygotes for ABCR mutations are predisposed to AMD but the data are conflicting. Studies of the genes responsible for autosomal dominant Sorsby fundus dystrophy, Doyne honeycomb retinal dystrophy, and Best disease have given negative results. In one large AMD family, linkage has been reported to markers in 1q25-q31. Recent data suggest that the ApoE epsilon4 allele may be associated with reduced risk of AMD. A better understanding of the genetic factors in AMD would contribute to understanding the pathogenesis. If those at risk could be identified it may be possible to modify lifestyle or develop novel therapies in the presymptomatic stage to prevent disease or decrease its severity.     

降钙素治疗延缓卵巢切除大鼠腰椎间盘退变

目的:观察降钙素对卵巢切除大鼠腰椎骨量及椎间盘退变的影响。方法:SD大鼠分为基线对照组、假手术组、卵巢切除组及降钙素治疗组,进行腰椎节段骨密度和骨形态计量学分析,观察椎间盘的组织形态学改变。结果:卵巢切除组骨量较对照组和降钙素治疗组显著下降,骨转化指标明显提高。降钙素治疗组的腰椎间盘组织学评分较卵巢切除组显著下降。结论:卵巢切除大鼠椎间盘退变可能是骨量减少引起的脊柱力学改变所致,降钙素治疗可以预防骨量丢失并延缓其腰椎间盘退变。     

Enhanced sprouting of retinotectal fibers after early superior colliculus lesions in hamsters treated with gangliosides

Summary The effects of exogenous gangliosides on sprouting of optic tract axons was studied in hamsters which, after a right tectal lesion on the day after birth (P1), had an abnormal retinotectal projection from the left eye to the left superior colliculus (SC). Sprouting of these axons was induced by removing the competing input by right eye removal on postnatal day 9 (P9). Intraperitoneal G_M1, given daily and started on P9, significantly stimulated the sprouting response. This was demonstrated by Fink-Heimer silver staining of anterograde axonal degeneration three days after the left eye was removed on P36. Terminal fields in the left SC were, in average, twice as large compared to controls. An estimate of the total number of terminals (silver stained particles) revealed a value of 7.9×10⁶ for G_M1 and 3.2×10⁶ for control hamsters, respectively. Diencephalic structures which also receive collateral input from the sprouting optic tract did not show any alterations in the size of the terminal field due to G_M1-treatment, suggesting that, in vivo, gangliosides fail to initiate sprouting in areas that have not previously been denervated. Unexpectedly, G_M1-treated hamsters also had significantly smaller right SC damage and less left damage near the midline. Subsequent reanalysis of the data based on a lesion-matching procedure indicates that effects on reducing atrophy were independent of the G_M1-enhanced sprouting of retinofugal axons. These findings provide the first direct evidence that exogenous G_M1 stimulates lesion-induced axon sprouting in the mammalian brain.     

NGF prevents further atrophy of cholinergic cells of the nucleus basalis due to cortical infarction in adult post-hypothyroid rats but does not restore cell size compared to euthroid rats

We have tested the hypotheses that nerve growth factor treatment in adult post-hypothyroid rats can: (1) restore cross-sectional area of cholinergic cells of the nucleus basalis and (2) prevent further atrophy of these neurons following cortical infaction. In addition, we assessed the expression of p75^NGFR and p140^trkA mRNAs in the nucleus basalis cells of post-hypothyroid rats. Rats were rendered hypothyroid by the addition of propylthiouracil to their diet beginning on embryonic day 19 until the age of 1 month. At this time both the pups and their dams continued to receive 0.05% propylthiouracil in their diet and the pups were thyroidectomized. At 60 days, propylthiouracil treatment was interrupted and thyroxine levels were restored to normal by daily subcutaneous administration of physiological levels of thyroxine. Morphometric analysis identified atrophied nucleus basalis magnocellularis cholinergic cells at two ages, days 75 and 105, identified by in situ hybridization for p75^NGFR and p140^trkA mRNAs in methylene blue stained cells (day 75) and choline acetyltransferase immunostaining (day 105). The mean number of silver grains (pixels) per μm² (mean±S.E.M.) of cell body cross-sectional area for p75^NGFR mRNA in the nucleus basalis magnocellularis of euthyroid rats was 3.43±0.89, which was not statistically different from post-hypothyroid animals (4.02±1.07). A similar finding was noted for p140^trkA mRNA: mean number of grains in the euthyroid group was 5.54±0.96 and was not statistically different from the post-hypothyroid group (6.32±1.45). Nerve growth factor treatment in adulthood (between days 75 and 82) did not restore cross-sectional area from early thyroid deprivation. However, it prevented further atrophy of nucleus basalis magnocellularis neurons following cortical devascularization inflicted in adulthood (day 75).     

Fertilization and early embryology: Effects of embryo density and co-culture of unfertilized oocytes on embryonic development of in-vitro fertilized mouse embryos

We have evaluated the effects of embryo density and the co-cultureof unfertilized (degenerating) oocytes on the development ofin-vitro fertilized (IVF) mouse embryos. In experiment 1, groupsof one, five, 10 or 20 zygotes were cultured in 20 µldrops of modified human tubal fluid (HTF) medium for 168 h at38.7°C in 5% CO₂ and 95% air. As the embryo density increased,significantly (P < 0.05) higher rates of embryos reachedhatched blastocyst stage. In addition, the time required forhatching after IVF was significantly (P < 0.05) shortenedby the increase in embryo density. In experiment 2, 10 IVF zygoteswere cultured with or without 10 unfertilized (degenerating)oocytes in 20 µl drops of HTF medium. The rates of IVFembryos that developed to morula, blastocyst, expanded blastocystand hatched blastocyst stages were decreased significantly (P< 0.01) by culturing embryos with unfertilized oocytes comparedwith culturing embryos alone. In experiment 3, groups of oneor 10 IVF zygotes or 10 IVF zygotes plus 10 unfertilized oocyteswere cultured in 20 µl drops of HTF medium and the numberof cells per blastocyst was examined at 120 h after IVF. Increasingembryo density resulted in a significant (P < 0.05) increasein the number of cells per blastocyst. In contrast, the cellnumber of IVF embryos that developed to blastocyst decreasedsignificantly (P < 0.05) when they were cultured with unfertilizedoocytes. The results suggest that in-vitro development of IVFmouse embryos is enhanced by increasing embryo density and isimpaired by co-culture with unfertilized (degenerating) oocytes.     

Ectodermal dysplasia,ectrodactyly and macular dystrophy (EEM syndrome) in siblings

We report a brother and sister with ectodermal dysplasia, ectrodactyly, and macular dystrophy (the EEM syndrome). Both children had abnormalities of the hands and the hair, and bilateral macular degeneration. The clinical picture in both is similar to, but less severe than, that described in the previously reported cases of this rare syndrome. Even though the parents are not related, they are both of Jewish Yemenite origin, and the possibility of a common ancestor cannot be ruled out. This would suggest autosomal recessive inheritance. The clinical picture in these patients suggests either variable expression or genetic heterogeneity in the EEM syndrome and further delineates the clinical and genetic spectrum of this condition. © 2001 Wiley‐Liss, Inc.