正常人群视网膜血氧饱和度的测量

目的 测量正常人群中的视网膜血氧饱和度。设计 观察性横断面研究。研究对象 纳入的正常受试者91例,其中男性37例,女性54例,平均年龄（37.5±14.0）岁。方法 对所有受试者进行全身及眼科检查,并采用视网膜血氧仪（Oxymap）测量视网膜血氧饱和度。选取鼻上、鼻下、颞上及颞下象限来分别进行视网膜血氧含量的测量,测量范围为距视盘边缘0.5个直径至3个视盘直径之间,选取象限内最粗的动脉和静脉。将视网膜动、静脉血氧饱和度作为因变量,眼部参数及全身系统性参数作为自变量进行多因素线性回归,分析视网膜动、静脉血氧饱和度与全身因素及眼部指标之间的相关性。主要指标 视网膜平均动脉血氧饱和度（SaO2-A）,视网膜平均静脉血氧饱和度（SaO2-V）,视网膜平均动静脉血氧饱和度差值（SaO2-AV）。结果 中国正常人群的视网膜平均SaO2-A为（92.1±7.2）%;视网膜平均SaO2-V为（52.5±6.6）%;视网膜平均SaO2-AV为（39.6±7.5）%。鼻上象限的SaO2-A、SaO2-V和SaO2-AV较高,分别为（98.5±10.1）%、（57.3±8.7）%和（41.3±11.9）%。在多因素分析中,与SaO2-A相关的系统性因素包括高龄（B=0.24,P=0.049）,高脂血症（B=0.26,P=0.018）。吸烟与SaO2-V的降低有一定的相关性（B=-0.25,P=0.033）;SaO2-V与年龄（P=0.665）、眼压（P=0.073）、舒张压（P=0.616）无显著相关性。SaO2-AV与年龄呈正相关（B=0.219,P=0.046）,与性别成负相关（B=-0.253,P=0.019）。结论 高龄人群的视网膜动脉血氧含量相对较高;吸烟可能会导致视网膜静脉血氧含量降低;视网膜动静脉血氧饱和度差值与年龄呈正相关;男性的视网膜动静脉血氧饱和度差值较大。（眼科,2016, 25： 339－342）     

Retinal histopathology of a carrier of X-chromosome-linked retinitis pigmentosa

Autopsy eyes were examined from a 79-year-old female carrier of X-chromosome-linked retinitis pigmentosa. At age 78 years, she had no visual symptoms but had intraretinal bone spicule pigmentation in the nasal and inferior periphery of both eyes. Rods, cones, and pigment epithelium in the central retina appeared normal. In the midperiphery, patches with advanced photoreceptor cell degeneration were observed overlying pigment epithelium containing melanolysosomes. Within these patches, rods and cones were reduced in number or absent, and pigment epithelial cells abutted the external limiting membrane. A precipitous decline in rod nuclei was observed in transitional zones between areas of apparently normal photoreceptors and areas of absent photoreceptors. In the far periphery, large areas lacked photoreceptors and pigment epithelium. Histopathologic findings in this elderly carrier are compared with those previously described in a 24-year-old man with X-chromosome-linked retinitis pigmentosa.     

Retinal vessel oxygen saturation in healthy subjects and early branch retinal vein occlusion

AIM: To measure the retinal oxygen saturation in healthy subjects and early branch retinal vein occlusion (BRVO) in Chinese population. METHODS: The retinal vessel oxygen saturation of the healthy subjects and BRVO patients were measured by a noninvasive retinal oximeter (Oxymap ehf., Reykjavik, Iceland). RESULTS: The study included 22 patients with unilateral BRVO (mean age: 55.1±8.8y) in the study group and 91 healthy participants (mean age: 37.5±14.0y) in the control group. In the healthy individuals, mean arterial and venous oxygen saturation were significantly (P<0.001) higher in the superior nasal quadrant (98.5%±10.1% and 57.3%±8.7%, respectively) than in the inferior nasal quadrant (94.2%±9.0% and 54.1%±9.6%, respectively), followed by the superior temporal quadrant (89.1%±10.1% and 51.9%±8.9%, respectively) and the inferior temporal quadrant (86.4%±9.4% and 46.6%±9.6%, respectively). In patients with ischemic BRVO, arterial oxymetric values were significantly higher and venous measurements significantly lower for the affected vessel (107.5%±9.7% and 46.4%±14.2%, respectively) than the unaffected vessel in the same eye (99.2%±12.2% and 55.5%±7.9%, respectively) and as compared to the vessel in the unaffected fellow eye (93.1%±6.9% and 55.7%±6.8%) (P=0.005 and P=0.02, respectively). In the patients with non-ischemic BRVO, mean venous oxygen saturation was lower in the affected vein (39.8%±12.2%) than in the unaffected vessels of the same eye (50.8%±10.5%) and in the fellow eye (58.21%±5.7%) (P=0.03). Mean arterial oxygen saturation did not differ significantly (P=0.42) between all three groups. CONCLUSION: In patients with BRVO, the venous oxygen saturation in the affected vessels is decreased potentially due to decreased blood velocity and flow. Interestingly, the arterial oxygen saturation in eyes with ischemic BRVO is increased in the affected arteries.     

Retinal degeneration and local oxygen metabolism

Vision loss due to various forms of outer retinal degeneration remains a major problem in clinical ophthalmology. Most retinal degenerations are precipitated by genetic mutations affecting the retinal pigment epithelium and sensory retina, but it is becoming increasingly evident that resultant metabolic changes within the retina may also contribute to the further progression of photoreceptor cell loss. In particular, a role for the local oxygen environment within the retina has been proposed. The correct balance between retinal oxygen supply and oxygen consumption in the retina is essential for retinal homeostasis, and disruption of this balance is a factor in many retinal diseases. In animal models of photoreceptor degeneration, manipulation of environmental oxygen levels has been reported to be able to modulate the rate of photoreceptor degeneration. Clinically, hyperbaric oxygen therapy has already been used in retinitis pigmentosa patients and other types of oxygen therapy have been proposed. It therefore seems appropriate to review our current understanding of the oxygen environment in the normal and degenerating retina, and to build a clearer picture of how the retinal oxygen environment can be modulated. We focus on techniques that have been, or may be, applied clinically, such as modulation of systemic oxygen levels and modulation of retinal oxygen metabolism by light deprivation. Data from direct measurements of intraretinal oxygen distribution in rat models at different stages of photoreceptor degeneration will be reviewed. These models include the Royal College of Surgeons (RCS) rat, and the P23H rat model of outer retinal degeneration. Microelectrode based techniques have allowed the intraretinal oxygen distribution to be measured as a function of retinal depth under well-controlled systemic conditions at different stages of the degeneration process. Both models showed changes in the intraretinal oxygen distribution during the degenerative period, with the changes reflecting the gradual loss of oxygen metabolism of the degenerating photoreceptors. This results in higher than normal oxygen levels in the remaining outer retina and a significant alteration in the oxygen flux from the choroid to the inner retina. The maintenance of normal oxygen levels in the inner retina implies that inner retinal oxygen uptake is well preserved, and that there is also reduced oxygen input from the deeper capillary layer of the retinal circulation. Choroidal oxygen tension and the oxygen tension in the pre-retinal vitreous were unaffected at any of the time periods studied prior to, and during, the degeneration process. It is well known that both hypoxia and hyperoxia can cause neural cell stress and damage. Logically, any therapeutic intervention based on oxygen therapy should attempt to restore the oxygen environment of the remaining retinal cells to within the physiological range. Before any oxygen based therapies for the treatment of retinal degeneration should be seriously considered, the oxygen environment in the degenerating retina should be determined, along with clinically usable methods to restore the oxygen environment to the critical cell layers.     

Flicker electroretinogram in retinitis pigmentosa

Electroretinograms (ERGs) were recorded as a function of flicker frequency from 5 to 50Hz for 14 retinitis pigmentosa (RP) patients, 12 normal subjects and 1 rod monochromat. Data were analyzed by measuring the angular position of the response maximum, i.e. the phase, as a function of pulse-train frequency. Flicker ERGs obtained from the RP patients showed non-linear, frequency-dependent phase shifts when compared to the normal data. These phase shifts were simulated in a normal observer by attenuating the stimulus luminance by 1 log unit. However, the shape of the waveforms recorded from the normal differed markedly from those recorded from the RP patients. The differences, but not the ratios of the times-to-peak of the positive and negative ERG wavelets were longer in the RP patients than in the normal. These data suggest that the temporal anomalies in the RP flicker ERG are most likely due to changes in the amplitudes and time constants of the ERG components, and not simply to a reduced quantum catch or photoreceptor loss.Supported by research and core facility grants from the National Institutes of Health (EY-01791 and EY-01765)     

视网膜色素变性的研究进展

视网膜色素变性(retinitis pigmentosa,RP)是常见的与遗传相关的致盲性眼病之一,随着人类基因图谱的成功建立,它成为近几年国内外基础医学和临床医学共同的研究热点。本文回顾十余年来国内外特别是国外相关文献,对视网膜色素变性的发病机制、治疗方法的研究进展作一综述。     

Genetic dissection of non-syndromic retinitis pigmentosa

Retinitis pigmentosa (RP) belongs to a group of pigmentary retinopathies. It is the most common form of inherited retinal dystrophy, characterized by progressive degradation of photoreceptors that leads to nyctalopia, and ultimately, complete vision loss. RP is distinguished by the continuous retinal degeneration that progresses from the mid-periphery to the central and peripheral retina. RP was first described and named by Franciscus Cornelius Donders in the year 1857. It is one of the leading causes of bilateral blindness in adults, with an incidence of 1 in 3000 people worldwide. In this review, we are going to focus on the genetic heterogeneity of this disease, which is provided by various inheritance patterns, numerosity of variations and inter-/intra-familial variations based upon penetrance and expressivity. Although over 90 genes have been identified in RP patients, the genetic cause of approximately 50% of RP cases remains unknown. Heterogeneity of RP makes it an extremely complicated ocular impairment. It is so complicated that it is known as “fever of unknown origin”. For prognosis and proper management of the disease, it is necessary to understand its genetic heterogeneity so that each phenotype related to the various genetic variations could be treated.     

Dominant ARL3-related retinitis pigmentosa

Purpose: To clinically and genetically characterise a second family with dominant ARL3-related retinitis pigmentosa due to a specific ARL3 missense variant, p.(Tyr90Cys).

Methods: Clinical examination included optical coherence tomography, electroretinography, and ultra-wide field retinal imaging with autofluorescence. Retrospective data were collected from the registry of inherited retinal diseases at Oslo university hospital. DNA was analysed by whole-exome sequencing and Sanger sequencing. The ARL3 missense variant was visualized in a 3D-protein structure.

Results: The phenotype was non-syndromic retinitis pigmentosa with cataract associated with early onset of decreased central vision and central retinal thinning. Sanger sequencing confirmed the presence of a de novo ARL3 missense variant p.(Tyr90Cys) in the index patient and his affected son. We did not find any other cases with rare ARL3 variants in a cohort of 431 patients with retinitis pigmentosa-like disease. By visualizing Tyr90 in the 3D protein structure, it seems to play an important role in packing of the α/β structure of ADP-ribosylation factor-like 3 (ARL3). When changing Tyr90 to cysteine, we observe a loss of interactions in the core of the α/β structure that is likely to affect folding and stability of ARL3.

Conclusion: Our study confirms that the ARL3 missense variant p.(Tyr90Cys) causes retinitis pigmentosa. In 2016, Strom et al. reported the exact same variant in a mother and two children with RP, labelled ?RP83 in the OMIM database. Now the questionmark can be removed, and ARL3 should be added to the list of genes that may cause non-syndromic dominant retinitis pigmentosa.     

视网膜色素变性1基因在常染色体显性遗传视网膜色素变性家系中的突变分析

目的:研究常染色体显性遗传视网膜色素变性(autosomal dominant retinitis pigmentosa,ADRP)家系中视网膜色素变性1(retinitis pigmentosa-1,RP1)基因的突变特征及其在RP发病机制中的作用。方法:运用聚合酶链反应和直接测序方法,对6个ADRP家系的47例成员和50例对照者进行了RP1基因全编码区和邻近剪切位点的内含子区域序列突变的筛选与检测。运用单因素分析、多因素Logistic回归分析研究RP1基因点突变在RP发病中的作用。结果:ADRP家系成员和对照组RP1基因第4外显子上检测出2个变异位点。在1691和1725密码子存在杂合的两种类型的密码子(S1691P,Ser-Pro,TCT→CCT;Q1725Q,Gln-Gln,CAA→CAG)。ADRP家系成员中Ser-1691-Pro及Gln-1725-Gln位点突变率显著高于正常对照组(χ2=11.202,P<0.05)。结论:RP1基因Ser-1691-Pro及Gln-1725-Gln位点多态性可增高RP的危险性,具有潜在的致病性,考虑为ADRP家系的易感基因。     

视网膜色素变性的实验研究进展

视网膜色素变性是一种遗传性眼病,遗传方式包括常染色体显性遗传、常染色体隐性遗传及性连锁隐性遗传等,目前已知的突变位点超过3 000个,造成本病临床治疗困难。眼科学者致力于探索视网膜色素变性的治疗方式,进行了大量实验研究,主要有药物治疗、细胞移植、基因治疗等治疗方式。药物治疗包括中药、抗氧化剂、抗凋亡剂、神经营养因子等,与其它治疗方式相比,无侵入性,且方便价廉,但其作用机制尚需更深入的研究。细胞移植被认为是治疗视网膜色素变性的有效方法,但有可能引起视网膜前膜及黄斑皱褶。基因治疗虽然存在一定的局限性,但随着基因编辑技术和新型基因递送载体的发展,未来会成为视网膜色素变性最有希望的治疗方式之一。本文对近年来视网膜色素变性的实验研究进行了综述与展望。     

Properties of electroretinographic intensity-response functions in retinitis pigmentosa

Dark-adapted electroretinogram (ERG) b-wave amplitudes and implicit times were recorded as a function of stimulus luminance for 15 retinitis pigmentosa (RP) patients and 15 normal subjects. B-wave amplitude as a function of log stimulus luminance was fit by non-linear regression with the Naka-Rushton equation, which has 3 independent parameters: The maximum response (R_max), slope (n) and half-saturation constant (K). B-wave implicit-time as a function of log stimulus luminance was fit by linear regression. Compared to normal, the RP R_max values were markedly reduced, suggesting response compression; the RP K values were elevated by an average of 0.76 log unit, suggesting relatively small losses in retinal sensitivity. There was no correspondence between R_max and visual field area for the RP patients (coefficient of correlation = -0.02). All but 2 of the 15 RP patients had normal or shallower-than-normal implicit-time intensity-response functions, indicating that over most of the dynamic range of the ERG, the implicit-times were either normal or faster-than-normal. These results are discussed in terms of possible RP disease mechanisms.Presented at the annual meeting of the Association for Research in Vision and Ophthalmology, Sarasota, Florida, 1981.Supported by research and core facility grants from the National Eye Institute (EY-01791 and EY-01765).Research to Prevent Blindness, Foreign Scholar Fellowship recipient; from Capital Hospital, Chinese Academy of Medical Sciences, Beijing, Peoples Republic of China.