Long-term follow-up of optic neuropathy in chronic low cerebrospinal fluid pressure monkeys: the Beijing Intracranial and Intraocular Pressure (iCOP) Study

Science China Life Sciences -     

Normative Values of Retinal Oxygen Saturation in Rhesus Monkeys: The Beijing Intracranial and Intraocular Pressure (iCOP) Study

Objective

To study the normal values of the retinal oxygen saturation in Rhesus monkeys and to evaluated repeatability and reproducibility of retinal oxygen saturation measurements.

Methods

Eighteen adult Rhesus macaque monkeys were included in this experimental study. An Oxymap T1 retinal oximeter (Oxymap, Reykjavik, Iceland) was used to perform oximetry on all subjects. Global arterial (SaO₂) and venous oxygen saturation (SvO₂), arteriovenous difference in SO₂ were measured. In the first examination, each eye was imaged three times. At the following two examinations, each eye was imaged once. All examinations were finished in one month. P values were calculated to evaluate the difference between the measurements during three visits by performing an ANOVA. Intra-visit and inter-visit intraclass correlation coefficient (ICC) was determined.

Results

At baseline, the average SaO₂ and SvO₂ were 89.48 ± 2.64% and 54.85 ± 2.18%, respectively. The global A-V difference was 34.63 ± 1.91%. The difference between the three visits was not significant (p>0.05). The highest A-V difference in SO₂ and lowest saturations were found in the inferotemporal quadrant. Intra-session and inter-visit repeatability were both high. For all oxygen saturation parameters, the ICC values of the intra-session repeatability ranged between 0.92 and 0.96. As found previously, a relatively high ICC value for inter-visit repeatability also was found for all oxygen saturation measurements, ranging between 0.86 and 0.94, with the lowest values in the infero-nasal quadrant.

Conclusions

Our study is the first to describe retinal SO₂ in healthy Rhesus monkeys. In normal monkey eyes, the reproducibility and repeatability of retinal oximetry oxygen saturation measurements were high in the retinal arterioles and venules. Our results support that Oxymap T1 retinal oximetry is a suitable and reliable technique in monkey studies.     

Finite element analysis of trans-lamina cribrosa pressure difference on optic nerve head biomechanics: the Beijing Intracranial and Intraocular Pressure Study

Science China Life Sciences - The present study aims to assess the potential difference of biomechanical response of the optic nerve head to the same level of trans-lamina cribrosa pressure...     

Intraocular Pressure and Estimated Cerebrospinal Fluid Pressure. The Beijing Eye Study 2011

Purpose

To examine a potential association between intraocular pressure (IOP) and cerebrospinal fluid pressure (CSFP) in a population-based setting.

Methods

The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years (range: 50–93 years). A detailed ophthalmic examination was performed. Based on a previous study with lumbar cerebrospinal fluid pressure (CSFP) measurements, CSFP was calculated as CSFP [mm Hg] = 0.44×Body Mass Index [kg/m²]+0.16×Diastolic Blood Pressure [mm Hg]–0.18×Age [Years].

Results

In multivariate analysis, IOP was associated with higher estimated CSFP (P<0.001; standardized correlation coefficient beta: 0.27; regression coefficient B: 0.20; 95% confidence interval (CI): 0.16, 0.24), after adjusting for thinner central corneal thickness (P<0.001; beta: 0.45; B: 0.04;95%CI: 0.04,0.04), smaller corneal curvature radius (P<0.001; beta:−0.11; B:−1.13;95%CI:−1.61,−0.64), shallower anterior chamber depth (P = 0.01; beta:−0.05; B:−0.33;95%CI:−0.59,−0.08) and longer axial length (P = 0.002; beta: 0.08; B: 0.20;95%CI: 0.08,0.32)), and after adjusting for the systemic parameters of higher pulse rate (P<0.001; beta: 0.08; B: 0.02;95%CI: 0.01,0.03), higher prevalence of arterial hypertension (P = 0.002; beta: 0.06; B: 0.32;95%CI: 0.12,0.53)), frequency of drinking alcohol (P = 0.02; beta: 0.04; B: 0.09;95%CI: 0.01,0.17), higher blood concentration of triglycerides (P = 0.001; beta: 0.06; B: 0.06;95%CI: 0.02,0.10) and cholesterol (P = 0.049; beta: 0.04; B: 0.08;95%CI: 0.00,0.17), and body mass index (P<0.001; beta:−0.13; B:−0.09;95%CI:−0.13,−0.06). In a parallel manner, estimated CSFP (mean: 10.8±3.7 mm Hg) was significantly associated with higher IOP (P<0.001; beta: 0.13; B: 0.18;95%CI: 0.13,0.23) after adjusting for rural region of habitation (P<0.001; beta:−0.37; B:−2.78;95%CI:−3.07,−2.48), higher systolic blood pressure (P<0.001; beta: 0.34; B: 0.06;95%CI: 0.05,0.07), higher pulse rate (P = 0.003; beta: 0.05; B: 0.02;95%CI: 0.01,0.03), taller body height (P<0.001; beta: 0.11; B: 0.05;95%CI: 0.03,0.07), higher blood concentration of cholesterol (P = 0.003; beta: 0.05; B: 0.17;95%CI: 0.06,0.28) and higher level of education (P = 0.003; beta: 0.09; B: 0.30;95%CI: 0.16,0.45).

Conclusions

IOP was positively associated with estimated CSFP after adjusting for other ocular and systemic parameters. As a corollary, higher estimated CSFP was significantly associated with higher IOP in multivariate analysis. It fits with the notion that the arterial blood pressure, estimated CSFP and IOP are physiologically correlated with each other.     

Five-Year Change in Intraocular Pressure Associated with Changes in Arterial Blood Pressure and Body Mass Index. The Beijing Eye Study

Purpose

To examine a potential association between longitudinal changes in intraocular pressure (IOP), arterial blood pressure and body mass index (BMI) in a population-based setting.

Methods

The longitudinal population-based Beijing Eye Study included 2355 subjects with an age of 45+ years who were examined in 2006 and in 2011. The participants underwent a detailed ophthalmic examination including tonometry and measurement of arterial blood pressure and BMI.

Results

Data on IOP, arterial blood pressure and BMI measured in 2006 and in 2011 were available for 2257 (95.8%) subjects with a mean age of 59.5±9.7 years. The mean change in IOP was −1.25±2.26 mm Hg, mean change in mean blood pressure −7.4±12.1 mmHg, and mean change in BMI was 0.01±2.04 kg/m². In multivariate analysis, the 5-year change in IOP was significantly associated with a higher change in mean blood pressure (P<0.001; standardized regression coefficient Beta:0.11; regression coefficient B:0.02; 95% confidence interval (CI):0.01,0.03) after adjusting for younger age (P<0.001;Beta:−0.18;B:−0.04;95% CI:−0.05,−0.03), shorter body stature (P = 0.002;Beta:−0.06;B:−0.06;95% CI:−0.03,−0.01), thicker central corneal thickness (P<0.001;Beta:0.19;B:0.02;95% CI:0.01,0.02), deeper anterior chamber depth (P = 0.01;Beta:0.05;B:0.33;95% CI:0.07,0.60), and lower intraocular pressure at baseline (P<0.001;Beta:−0.56;B:−0.42;95% CI:−0.45,−0.39). If the analysis included only longitudinal parameters, the change in IOP was significantly associated with a higher change in mean arterial blood pressure (P<0.001;Beta:0.10;B:0.02;95% CI:0.01,0.03) and a higher change in body mass index (P<0.04;Beta:0.04;B:0.04;95% CI:0.01,0.09).

Conclusions

In the 5-year follow-up of our population-based sample, a change in IOP was associated with a corresponding change in arterial blood pressure and with a corresponding change in body mass index. These longitudinal data support the notion of a physiological relationship between arterial blood pressure, intraocular pressure and body mass index. These findings may be of interest for the discussion of the pathogenesis of glaucomatous optic neuropathy.     

Intraocular Pressure and Associations in Children. The Gobi Desert Children Eye Study

Purpose

To assess the intraocular pressure (IOP) and its association in children in a population living in an oasis in the Gobi Desert.

Methods

The cross-sectional school-based study included all schools in the Ejina region. The children underwent an ophthalmic examination, non-contact tonometry and measurement of blood pressure and body height and weight.

Results

Out of eligible 1911 children, 1565 (81.9%) children with a mean age of 11.9±3.5 years (range: 6–21 years) participated. Mean spherical refractive error was −1.58±2.00 diopters. In multivariate analysis, higher IOP (right eye) was associated with younger age (P<0.001; standardized coefficient beta: −0.13; regression coefficient B: −0.13; 95% Confidence interval (CI):−0.18, −0.07), higher diastolic blood pressure (P<0.001;beta:0.13;B:0.05;95%CI:0.03,0.07), higher corneal refractive power (P<0.001;beta:0.11;B:0.23;95%CI:0.12,0.34), more myopic refractive error (P = 0.035;beta: −0.06;B: −0.10;95%CI: −0.19, −0.001), and Han Chinese ethnicity of the father (P = 0.03;beta:0.06;B:0.42;95%CI:0.04,0.89). If age and diastolic blood pressure were dropped, higher IOP was associated with higher estimated cerebrospinal fluid pressure (CSFP) (P<0.001;beta:0.09; B:0.13;95%CI:0.06,0.21) after adjusting for higher corneal refractive power (P<0.001) and Han Chinese ethnicity of the father (P = 0.04). Correspondingly, higher IOP of the left eye was associated with younger age (P<0.001;beta: −0.15;B: −0.16;95%CI: −0.21, −0.10), female gender (P<0.001;beta:0.09;B:0.65;95%CI:0.30,1.01), higher corneal refractive power (P<0.001;beta:0.08;B:0.19;95%CI:0.06,0.32), more myopic refractive error (P = 0.03;beta: −0.06;B: −0.12;95%CI: −0.22, −0.01), and higher estimated CSFP (P<0.001;beta:0.11;B:0.17;95%CI:0.09,0.24).

Conclusions

In school children, higher IOP was associated with steeper corneal curvature and with younger age and higher blood pressure, or alternatively, with higher estimated CSFP. Corneal curvature radius should be included in the correction of IOP measurements. The potential association between IOP and CSFP as also assumed in adults may warrant further research.     

Activating transcription factor 3 (ATF3) expression in the neural retina and optic nerve of zebrafish during optic nerve regeneration

Fish, unlike mammals, can regenerate axons in the optic nerve following optic nerve injury. We hypothesized that using microarray analysis to compare gene expression in fish which had experienced optic nerve lesion to fish which had undergone a similar operation but without optic nerve injury would reveal genes specifically involved in responding to optic nerve injury (including repair), reducing detection of genes involved in the general stress and inflammatory responses. We discovered 120 genes were significantly (minimally two-fold with a P-value ≤ 0.05) differentially expressed (up or down) at one or more time point. Among these was ATF3, a member of the cAMP-response element binding protein family. Work by others has indicated that elevated cAMP could be important in axon regeneration. We investigated ATF3 expression further by qRT-PCR, in situ hybridization and immunohistochemistry and found ATF3 expression is significantly upregulated in the ganglion cell layer of the retina, the nerve fiber layer and the optic nerve of the injured eye. The upregulation in retina is detectable by qRT-PCR by 24 h after injury, at which time ATF-3 mRNA levels are 8-fold higher than in retinas from sham-operated fish. We conclude ATF3 may be an important mediator of optic nerve regeneration-promoting gene expression in fish, a role which merits further investigation.     

神经电生理在颅内动脉瘤夹闭术中联合颅内压、脑灌注压监测的应用效果研究

摘要 目的：探讨神经电生理在颅内动脉瘤夹闭术中联合颅内压（ICP）、脑灌注压（CPP）监测的应用效果。方法：选取2018年12月～2020年1月我院进行开颅手术治疗的颅内动脉瘤患者60例,采用简单随机化分组方法分为两组,每组30例。对照组实施颅内动脉瘤夹闭手术,观察组在对照组基础上,术中应用神经电生理、ICP、CPP监测。比较两组动脉瘤夹闭情况,术后第1 d新发神经功能缺损情况,术前、术后1 d、术后3个月格拉斯哥昏迷评分（GCS）、美国国立卫生研究院脑卒中量表（NIHSS）评分及术后3个月预后优良率。结果：两组动脉瘤均完全夹闭,观察组术后第1 d新发神经功能缺损率6.67%（2/30）低于对照组的26.67%（8/30）（P＜0.05）;术后1 d观察组GCS评分高于对照组,NIHSS评分低于对照组（P＜0.05）;排除失访病例后,观察组术后3个月GOS分级、mRS分级优良率分别为88.89%、88.89%,与对照组的88.00%、84.00%比较,差异无统计学意义（P＞0.05）。结论：采用神经电生理联合ICP、CPP监测,能够实时掌握颅内动脉瘤夹闭术患者脑组织血流情况,根据监测结果及时采取相应干预措施,可预防不可逆的脑缺血改变,改善术后早期患者意识状态,减少术后早期神经功能缺损的发生。     

Changes in retinal and choroidal morphology after cerebrospinal fluid pressure reduction: a Beijing iCOP study

正Dear Editor,Glaucoma is a multifunctional neurodegenerative disease and is the leading cause of irreversible blindness. It is characterized by progressive loss of retinal ganglion cells and their axons leading to visual field defects. Two mechanisms of glaucomatous optic nerve damage have been     

The lipofuscin in neuroglial cells of the optic nerve of Formosan rock-monkey (Macaca cyclopis)

The ultrastructure of lipofuscin granules in neuroglial cells of the optic nerve of the Formosan Rock-Monkey was investigated by electron microscopy. In the cytoplasm of astroglial cells, numerous irregular lipofuscin granules were characterized by the presence of large lipid droplets, small electron-dense pigment granules, and some lamellar structures. The lipofuscin granules of the oligodendroglial cells were composed largely of dense, coarse pigment granules, multilinear structures, and a few small lipid droplets. The lipofuscin granules in microglial cells were characterized by numerous lipid droplets in various sizes, small electron-dense pigment granules, and prominent lamellar structures. It was reported that the lipofuscin granules are wear-and-tear materials and products from the cells in lower functional activity. However, our observations suggest that the presence of lipofuscin granules in the neuroglial cells of the optic nerve is likely a characteristic product of active phagocytosis.     

The influence of optic nerve section on blood metabolite levels in Carcinus maenas (Crustacea: Brachyura)

• 1.1. Blood metabolite levels were assayed in Carcinus maenas as an indicator of the functioning of the hyperglycemic hormone, HGH, secreted by the crab's eyestalk neuroendocrine tissue.
• 2.2. Bilateral eyestalk ablation eventually resulted in a hypoglycemic response after 2–3 days.
• 3.3. Bilateral optic nerve section produced a significant, long-term hypoglycemic response suggesting that release of HGH from the eyestalk sinus gland is controlled, via a promotive neural pathway, by the CNS and probably by the cerebral ganglia.
• 4.4. Injection of eyestalk extract into operated crabs consistently produced significant, short-term hyperglycemia.

     

Ingrowth of optic nerve fibers and onset of myelin ensheathment in the optic tectum of the trout (Salmo gairdneri)

Summary The early differentiation of the optic pathway of the trout was studied by means of autoradiography, silver impregnation and electron microscopy. Ingrowth of optic nerve fibers into the optic tectum was consistently shown by tracer application and Golgi studies to occur at stage 28, about one week before hatching. Fibers being arranged in discrete bundles were rapidly growing through the longitudinal axis of tectum and at stage 33 reached its posterior end. Cross sections of these fiber bundles at different positions revealed myelin ensheatment to be initiated at the end of stage 34 at the anterior pole of the tectum. Since in the optic nerve of the trout the onset of myelination occurred even earlier (stage 33), it is assumed that this differentiation process follows a rostro-caudal gradient during development of the optic pathway.     

Identification and morphometric evaluation of the synapses of optic nerve afferents in the optic tectum of the axolotl (Ambystoma mexicanum)

Summary The terminals of retinal afferents in the tectum of the axolotl have been identified ultrastructurally using techniques of horseradish peroxidase-filling and degeneration. The mitochondria in filled structures show a characteristic electron-lucent matrix. After both eyes have been removed, terminals with light mitochondria disappear from the area known to receive an optic input. In this area the presence of light mitochondria is almost always diagnostic of the retinal origin of a bouton. The synapses are similar to those assumed to be of retinal origin in other vertebrates. Detailed morphometric analysis has been carried out on identified optic synapses in the optic tectum of the axolotl.     

The differentiation of oligodendrocytes in the rat optic nerve

The time of appearance and the rate of accumulation of specific myelin lipids and proteins were measured in the rat optic nerve during the period from birth to 18 days. The appearance of the activities of several enzymes involved in the synthesis of these lipids was also monitored. Correlation of these biochemical data with previously known morphological findings indicated that the “active” oligodendrocytes (detected between 5 and 15 days after birth) displayed maximal levels of synthesis of the components of myelin, and that these cells appeared to be responsible for the initial synthesis of myelin. Both young and mature oligodendrocytes showed limited capacity to synthesize these compounds. Furthermore, induction of the enzymes involved in the synthesis of myelin components appeared to take place in a simultaneous, rather than a sequential manner.     

Pattern of structural differentiation in the optic nerve of trout (Salmo gairdneri)

Summary The development of the trout optic nerve is quantitatively described from early ontogenesis into adulthood. The nerve is oval in cross section until stage 34, thereafter the formation of vertically aligned parallel folds can be observed and thus the unique shape of a folded ribbon is gradually attained. Quantitative measurements revealed a linear increase in cross sectional area, caused in part by the formation of new folds and in part by an increase in size of the preexisting ones. We attribute the continuous expansion of individual folds to an increase in fiber size subsequent to myelination rather than to the addition of new fibers. The total number of glial cells increased concomitantly per fold.Myelinogenesis starst at stage 33 with the ensheathement of axons beginning at the dorsal edge of the primary fold and follows a highly ordered pattern throughout development, strictly succeeding neural outgrowth. The functional significance of this pattern is discussed.     

Polarized-light sensitivity in rainbow trout (Oncorhynchus mykiss): characterization from multi-unit responses in the optic nerve

Integrated spike activity of axons from the optic nerve was measured in an investigation of the e-vector sensitive mechanism underlying the ability of rainbow trout (Oncorhynchus mykiss) for orientation in downwelling, linearly-polarized light. In anaesthetized, immobilized fish, one eye was exposed to incremental light flashes which were superimposed over closely controlled background conditions. Under scotopic and various photopic conditions, intensity/response curves were generated from the on-response of the optic nerve. Relative sensitivity curves were then obtained as a function of e-vector direction for the 5 kinds of receptor cells in this trout's retina: rods, ultraviolet cones (UV), short wavelength cones (S), medium wavelength cones (M), and long wavelength cones (L).Under scotopic conditions, no sensitivity to e-vector was apparent: thus, rods do not mediate polarization sensitivity. Under photopic conditions, parr weighing 8–10 g exhibited e-vector sensitivity in two orthogonal channels. A UV stimulus (380 nm) on a white background evoked a three-peaked response (0°, 90°, and 180°) to the e-vector orientations presented in 30° increments between 0° and 180°. In contrast, when the background was illuminated with appropriate short and long wavelength cut-off filters, M-and L-cones showed maximum responses only to the horizontal (90°) plane whether they were stimulated at their -absorption band or their -absorption band in the near UV. Isolated UV-cones gave maximum responses to the vertical (0° and 180°) e-vector, thus corresponding to a second channel. The blue sensitive, S-cones, did not show evidence of polarization sensitivity. As well, no evidence of the polarization sensitivity was observed under UV isolating background conditions in larger individuals, 50–78 g smolts, although the other cone mechanisms responded as in smaller individuals.