Some observations on the zinc metabolism of the rabbit lens

Rabbits' lenses contain about 100 mumol kg-1 wet wt (145 mumol kg-1 water) of zinc. This metal appears to be quite uniformly distributed throughout the organ and more than 90% is firmly incorporated into the tissue so as not to be readily exchangeable. The concentration of Zn in the aqueous and vitreous humors is about 10(-5) M (one-fourth the concentration in the blood serum). Lenses incubated in vitro can accumulate Zn from solutions containing this concentration of the metal. This process is concentration-dependent and is increased following damage produced by metabolic inhibitors. The process probably involves diffusion and is increased in the presence of a low external calcium concentration and the Ca ionophore A 23187. Amino acids which are known to bind zinc did not influence its accumulation by the lens, with the exception of cystine which increased it. Accumulated Zn (using 65Zn as a tracer) was able to leave the lens, but this process was quite slow and was reduced by the presence of lanthanum and low Ca concentrations. It is suggested that Ca and Zn may share common binding sites in the tissue, and they could be utilizing the same channels to cross the cell membrane.     

Observations on high and low voltage compartments in the crystalline lens of the frog.

A range of electrical potentials could be measured in the frog lens. The most frequently measured potentials were ～?30 and ～?70 mV, with the latter being more predominant. These potentials were designated low and high potential compartments, respectively. The low and high potential compartments depolarized by 18 and 27 mV respectively, when the potassium concentration in the bathing solution was increased from 2·5 to 25 mm. The high potential compartments consistently depolarized when the lens was bathed in calcium-free solutions, whereas certain low potential compartments depolarized and others hyperpolarized. These findings suggested that both the high and low compartment potentials are membrane potentials of lens fibres with different ionic permeability properties.The depolarization of the high and low potential compartments in 25 mm potassium solution had identical time courses with half-times of approximately 100 sec. It can be inferred from these observations that both the high and low compartment membranes lie close to the surface of the lens.A number of low compartment potentials exhibited a rapid hyperpolarizing jump in potential following depolarization to about ?15 mV by either high potassium or calcium-free solutions. The behaviour of the potential subsequent to the jump suggested that the compartment had changed from a low to a high potential compartment.     

Engineering the crystalline lens with a biodegradable or non-degradable scaffold

Both a biodegradable hyaluronic acid (HA) and a nondegradable polymeric gel were evaluated as scaffolds for tissue engineering the lens in Dutch Belt pigmented and New Zealand white rabbits. Following removal of the crystalline lens through a 2 mm capsulorhexis, a collagen patch or a silicone plug was placed in the capsule bag to seal the capsulotomy. In Part I, a cross-linked HA or cohesive solution of HA was injected into the capsule bag. In Part II, a synthetic polymer (SP) was injected into the capsular bag of one eye and HA followed by SP (HA/SP) was injected into the capsule bag of the opposite eye. At 3 months focal Nd:YAG laser photocoagulation was performed in an attempt to remove some retained HA gel in one eye. Overall the regenerated lenses of the HA gel groups were spherical with excellent cortical structure and clarity and a spherical nucleus of condensed HA gel. In the one eye treated with focal photocoagulation, partial clearing of the retained HA gel was noted. In the SP and HA/SP eyes, lens regrowth around the polymer was generally clear in the anterior and peripheral capsule bag and more opacified posterior to the polymeric scaffold. In summary, naturally regenerating lens tissue was directed to grow in a more normal, regular pattern by providing a biodegradable hyaluronic acid scaffold or a nondegradable polymeric optical scaffold.     

The optical properties of the crystalline lens and their significance

We do not yet have definitive data on the optical structure of the lens, including surface shapes and gradient refractive index distribution. Some data do exist but we need much more data to complete our knowledge of this structure. However, using current and sparse knowledge, we can use mathematical modelling to study the effects of surface shapes and gradient refractive index structure on the Gaussian and aberration properties of the lens. The equations extracted from this modelling show some interesting results, for example, the way the gradient index structure provides some of the refractive power and how this structure possibly predicts a negative spherical aberration of the lens, which is observed in real eyes. This modelling will provide a firm theoretical foundation for analysing more accurate and extensive lenticular shape and refractive index data as they become available.     

Cytoplasmic filaments in the crystalline lens of various species: functional correlations.

The distribution of cytoplasmic filaments in lenses of five species was studied with the electron microscope. Two distinct patterns emerged. One pattern, in which filaments are grouped in characteristic bundles around the nucleus, in processes, and throughout the subcortical cytoplasm of epithelial cells, is typical of spherical, non-accommodating lenses of mice and rats. The second pattern is associated with anteriorly-flattened, accommodating lenses of infant human, squirrel and frog. In these, filaments are scattered in epithelial cells, but are accumulated on either side of the plasma membrane junction between epithelial cells and lens fibers. They are especially dense on the lens fiber side of the junction, and form a lattice associated with the lens fiber plasma membrane. The lattice is less extensive along the sides of lens fibers not in contact with epithelial cells. In spherical lenses the epithelial-fiber lattice is greatly reduced. Filaments in both types of lenses ranged in diameter between 5 and 11 nm. The filaments are thought to be a mixture of thin and intermediate filaments.It is hypothesized that the role of cytoplasmic filaments in lens, depending on the pattern present, is either to structurally support a spherical shape, or to provide a contractile force or elasticity to return the flattened anterior surface to the accommodated state in conjunction with the elasticity of the lens capsule.     

玻璃体切除联合晶状体超声粉碎在合并晶状体脱位眼外伤中的应用研究

目的:探讨玻璃体切除联合晶状体超声粉碎在合并晶状体脱位眼外伤中的应用。方法:选择我院眼科中心2a余接受不同手术方式治疗眼外伤合并晶状体脱位的40例40眼受术者资料,并对其术中并发症,术后视力、眼压等进行统计分析。术后随访时间3mo～2a;结果:行"玻璃体切除联合晶状体经角膜缘取出术"19例19眼中1例1眼因视神经挫伤术后矫正视力不提高未植入人工晶状体,其余18例18眼均植入后房型人工晶状体,其中疗效显著者8例8眼(44%),有效者5例5眼(28%),效果欠佳者5例5眼(28%)。行"玻璃体切除联合晶状体超声粉碎术"21例21眼中2例2眼因视神经挫伤术后矫正视力不提高未植入人工晶状体,其余19例19眼均植入后房型人工晶状体,其中疗效显著者16例(84%),有效者2例2眼(11%),效果欠佳者1例1眼(5%)。两组疗效显著者比较具有统计学意义(χ2=4.787,df=1,P=0.029<0.05),术中无并发症发生。"玻璃体切除联合晶状体经角膜缘取出术"中并发症视网膜损伤,5例5眼(26.32%),两组比较具有统计学意义(χ2=4.193,P=0.042<0.05),球内出血3例3眼(16%),两者比较具无统计学意义。结论:"玻璃体切除联合晶状体超声粉碎术"可使眼外伤合并晶状体脱位患者眼球在密闭条件下进行手术,且可将对眼球组织的损伤进一步减小,从而很大程度上挽救和提高了患者的视力。     

Internal deformation of the human crystalline lens during accommodation

Purpose: To describe the internal deformations in the crystalline lens that occur during accommodation. Methods: A computer‐based mechanical model of accommodation was created using the finite element method. The lens geometry of the model was based on in vivo measurements of human lenses in the accommodated state. The mechanical properties of the lens were based on ex vivo measurements of human lenses. To achieve a state of disaccommodation, the lens equator was stretched by 7%. The internal strains and displacements were calculated for a young accommodating lens, a lens of pre‐presbyopic age and a lens of presbyopic age (20, 40 and 60 years old, respectively). Results: The model showed that the radial strain was maximal in the nucleus for the young accommodating lens and minimal in the nucleus for the oldest non‐accommodating lens. In the young lens the deformations occurred throughout the entire lens, whereas in the older non‐accommodating lens the deformations were concentrated in the equatorial region. Conclusions: The model predicted that during accommodation, changes in lens thickness are mainly caused by deformation of the nucleus. In the older, non‐accommodating lens, the deformations occur predominantly in the equatorial region and do not affect the central curvatures of the lens.     

Calcium metabolism of the rabbit lens

The Ca concentration in the rabbit lens is less than that in its bathing aqueous and vitreous humors. This Ca is not distributed evenly in the tissue; it has a higher concentration in the outer peripheral than the inner parts of the organ. About 60% of the total lenticular Ca is present in a layer extending about 0·5 mm down from the outer surface (25% of the total tissue in the lens). When incubated in a solution containing ⁴⁵Ca about 40% of the lenticular Ca readily exchanges with the isotope in 3 hr; no further change occurred over the next 21 hr. This exchange appeared to occur across either the anterior or posterior side of the lens. The accumulated ⁴⁵Ca was found to be present in a surface layer about 1 mm deep. The remaining 60% of the lenticular Ca was difficult to displace. Incubation for 5 hr in a Ca-free solution containing EDTA or following freezing and thawing resulted in a loss of only an additional 20% of tissue Ca. The remaining ‘immobilizable’ Ca (40%) was present in both the nuclear and peripheral zones of the lens. When the Ca concentration of the external medium is raised, lens Ca rises also, and when the external concentration is reduced the tissue level declines. In the presence of metabolic inhibitors (iodoacetate plus cyanide) lenticular Ca rises. This effect is slow; little change was seen in 5 hr. Ca accumulation in the lens was enhanced by the Ca ionophore A23187 but an effect was not detectable in 5 hr. Incubation in Na-free media or ouabain did not influence Ca accumulation suggesting that a CaNa exchange is not involved in regulation. Quercetin and orthovanadate, which can inhibit Ca-activated ATPase in some tissues were without effect on lens calcium. The phenothiazine trifluoperazine (TFP), however, enhanced accumulation of Ca. Efflux of accumulated ⁴⁵Ca from the lens was rapid; 60% in 10 min and 90% in 3 hr. Lanthanum reduced the latter to 60% loss. Efflux of Ca from the lens was unchanged, under experimental conditions, by metabolic inhibitors, by EGTA, verapamil, TFP and vanadate.     

Glycero- versus sphingo-phospholipids: correlations with human and non-human mammalian lens growth

The human lens differs from other mammalian lenses in its very slow growth and unusual phospholipid composition of its cell membranes. Dihydrosphingomyelins (DHSMs) make up about half of all phospholipids in adult human fiber membranes. In all other membranes, sphingomyelins(SMs) with a trans double bond in their backbone, are prevalent. In our quest to understand the biological implications of such elevated DHSM levels, we analyzed membranes from various regions of human, elephant, giraffe, polar bear, pig and cow lenses. The levels of DHSMs were minor in non-human lens membranes. A strong correlation was observed between growth rate and relative contents of phosphatidylcholines(PCs) in epithelia and outer cortical fibers. Sphingomyelins became increasingly predominant in differentiated fibers and this increase was age dependent. Indeed, nuclear fiber membranes of aged non-human mammals were composed, almost exclusively, of (SMs). Although human lens membranes followed comparable compositional trends, the magnitude of the changes was much smaller. We postulate that the high relative contents of DHSMs provide a biochemically inert matrix in which only small amounts of PCs and SMs and their metabolites, known to promote and arrest growth, respectively, are present. This compositional difference is proposed to contribute to the slow multiplication and elongation of human lens cells.     

The influence of calcium-free solutions upon permeability characteristics of the rabbit lens.

Sodium, potassium and chloride content, potential difference and ⁸⁶Rb efflux rate constants were measured in rabbit lenses bathed in normal or calcium-free EGTA solution. The absence of calcium in the bathing solution resulted in a rapid depolarization of the lens potential, and a two-fold increase in the ⁶⁸Rb efflux rate. These changes were not due to the alteration of the ion distribution between the lens and its environment in the calcium-free solution, and the increase in the ⁶⁸Rb efflux rate could be explained on the basis of the depolarization alone. The magnitude of the calcium-free induced depolarization was not diminished when the lens active transport was inhibited by ouabain, but was significantly reduced when part of the sodium in the bathing solution had been replaced by sucrose. These observations suggested that one of the early effects of removal of calcium from the bathing solution is a rapid elevation of lens sodium permeability.     

The mechanisms of calcium homeostasis and signalling in the lens

Excessive Ca²⁺ can be detrimental to cells and raised levels of Ca²⁺ in human lenses with cortical cataract have been found to play a major role in the opacification process. Ca²⁺ homeostasis is therefore, recognised as having fundamental importance in lens pathophysiology. Furthermore, Ca²⁺ plays a central role as a second messenger in cell signalling and mechanisms have evolved which give cells exquisite control over intracellular Ca²⁺ ([Ca²⁺]_i) via an array of specialised regulatory and signalling proteins. In this review we discuss these mechanisms as they apply to the lens. Ca²⁺ levels in human aqueous humour are approximately 1 mM and there is a large, 10,000 fold, inwardly directed gradient across the plasma membrane. In the face of such a large gradient highly efficient mechanisms are needed to maintain low [Ca²⁺]_i. The Na⁺/Ca²⁺ exchanger (NCX) and plasma membrane Ca²⁺-ATPase (PMCA) actively remove Ca²⁺ from the cells, whereas the sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) sequesters Ca²⁺ in the endoplasmic reticulum (ER) Ca²⁺ store. In lens epithelial cells the dominant role is played by the ATPases, whilst in the fibre cells NCX activity appears to be more important. Usually, [Ca²⁺]_i can be increased in a number of ways. Ca²⁺ influx through the plasma membrane, for example, is mediated by an array of channels with evidence in the lens for the presence of voltage-operated Ca²⁺ channels (VOCCs), receptor-operated Ca²⁺ channels (ROCCs) and channels mediating store-operated Ca²⁺ entry (SOCE). Ca²⁺ signalling is initiated via activation of G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTK) of which the lens expresses a surprisingly diverse array responding to various neurotransmitters, hormones, growth factors, autocoids and proteases. Downstream of plasma membrane receptors are IP₃-gated channels (IP₃Rs) and ryanodine receptors (RYRs) located in the ER, which when activated cause a rapid increase in [Ca²⁺]_i and these have also been identified in the lens. Through an appreciation of the diversity and complexity of the mechanisms involved in Ca²⁺ homeostasis in normal lens cells we move closer to an understanding of the mechanisms which mediate pathological Ca²⁺ overload as occurs in the process of cataract formation.     

晶状体矢高对有晶状体眼后房型人工晶状体植入术后拱高的影响

目的:研究眼前节光学相干断层扫描(AS-OCT)所测量的晶状体矢高(CLR)与眼前节参数的关系,及CLR对有晶状体眼后房型人工晶状体植入术(PPC-ICL)术后拱高的影响。方法:本次研究为回顾性研究。选取2017-07/2018-07在安徽医科大学第二附属医院眼科行PPC-ICL患者40例80眼,采用超声生物显微镜测量眼的水平睫状沟直径(hSTS)及晶状体曲率(LC),Pentacam眼前节分析仪测量水平白到白直径(hWTW)、前房深度(ACD)及术后拱高。AS-OCT测量CLR和水平径线的两虹膜角膜夹角连线(ATA)。结果:CLR与ACD(r=-0.706,P<0.01)、术后1a的拱高(r=-0.509,P<0.01)负相关,CLR与LC正相关(r=0.667,P<0.01),与hWTW(r=0.123,P=0.275)、ATA(r=0.208,P=0.065)、hSTS(r=0.147,P=0.194)无相关性,而ACD与术后1a拱高有正相关性(r=0.680,P<0.01)。结论:CLR与ACD、LC有明显相关性,对PPC-ICL术后拱高的预测有一定作用。     

Refractive index of the crystalline lens in young and aged eyes

Background : When the ageing crystalline lens is modelled on the basis of a constant equivalent lens, the changes in ocular dimensions would lead to an increase in power of the order of two dioptres. A comparable increase in myopia is usually not evident with increasing age and this inconsistency has been referred to as the lens paradox. It has been proposed that this paradox can be resolved if the refractive index is modelled as a gradient refractive index. The purpose of this paper was to study differences in the equivalent, gradient and surface refractive index of the crystalline lens between a young and old age group. Methods : Biometric data was collected for 96 subjects: 48 young adults with an age range 19 to 31 years (mean 22.10 ± 2.93 years) and 48 old adults with an age range 49 to 61 years (mean 53.88 ± 3.88 years). The equivalent refractive index was determined for each subject by paraxial ray tracing and a merit function based on refractive error and Purkinje image height. The refractive index gradient was determined by modelling the crystalline lens as a bi-elliptical iso-indicial structure in a three-surface Gullstrand-Emsley schematic eye and a merit function based on the surface power, the gradient refractive index power and the equivalent power of the lens. The central refractive index of the lens was assumed to be 1.406. Results : The differences between the groups included a decrease in the mean equivalent refractive index from 1.427 ± 0.007 to 1.418 ± 0.006, an increase in surface refractive index from 1.386 ± 0.007 to 1.394 ± 0.006 with a concurrent change in the gradient refractive index profile. The refractive index changes maintained a constant mean lens power in each group. Conclusions : The so-called ‘lens paradox’ whereby an increase in the power of the crystalline lens does not lead to an increase in myopia is resolved by a decrease in the equivalent refractive index of the lens or when modelled as a gradient refractive index structure, by an increase in the surface refractive index and an associated change in gradient for an assumed central refractive index of 1.406.     

Intralenticular water interactions with phosphates in the intact crystalline lens

Since the ATP molecule is associated with the intracellular milieu, which consists mainly of water, this study suggests an intimate intracellular association with water molecules. Intact canine crystalline lenses (n = 6) were incubated at 37 degrees C in a buffer containing a pure D2O solvent and examined by [31P]-nuclear magnetic resonance (NMR) spectroscopy. Control lenses (n = 6) from contralateral eyes were incubated in a pure H2O-based buffer. During the first 4 h of a 24-hour incubation, the D2O-incubated lens maintained its phosphorus metabolic profile, indicating that the tissue maintains its metabolic health. During this period, however, the spectral signal widths of ATP narrowed progressively. Spectral-simulation analysis of ATP alpha-, beta- and gamma-phosphate signals revealed that the gamma-phosphate signal was narrowed significantly in contrast to the alpha-phosphate signal. Such differential signal narrowing within a single NMR spectrum indicates that the principal intracellular site of water hydrogen binding to the ATP molecule is at the gamma-group phosphate.     

Phospholipase C-induced "Na-channels" in the crystalline lens.

When present on the posterior side of the lens (in vitro in a divided Ussing-type chamber) phospholipase C increased translenticular p.d. and short-circuit current (SCC) while on the anterior it decreased these parameters. The electrical resistance, $\text{Δ}\text{p.d.}\text{Δ}\text{SCC}$, was unchanged. These effects were absent or reduced when the side of the lens exposed to the enzyme was bathed with Na-free, choline Ringer. On the posterior, the enzyme increased Na flux from the posterior to anterior bathing solutions but the Na flux in the opposite direction was unchanged. On the anterior it had the converse effect. Fluxes of K and Cl were unaffected. The enzyme increased the intracellular accumulation of Na when present on either side. Lithium could partly substitute for Na as the effects on p.d. and SCC were still seen. The results are of interest both with respect to the mechanism of Na movement across the lens and the possible nature of “Na-channels” in membranes.     

Sugar metabolism in the crystalline lens

Research on the sugar metabolism of the crystalline lens, past and present, is reviewed. The chief energy source in the lens is the Embden-Meyerhof pathway; respiration and oxidative phosphorylation become more important as the lens ages. The function of the α-glycerophosphate cycle is not fully understood. The mechanisms involved in cataract formation, including those of hypoglycemic cataract and osmotic cataracts, are discussed. Sugar cataracts can be delayed or prevented with such aldose reductase inhibitors as flavonoids. By inhibiting aldose reductase, the formation and accumulation of sugar alcohols is stopped. This approach may be useful as a medical therapy for human diabetic senile cataracts.     

脱位于玻璃体腔的晶状体碎核切除手术

目的 观察应用玻璃体切割头联合导光纤维头手法碎核摘除玻璃体腔脱位晶状体的效果.方法 对Ⅲ级及以下核晶状体脱位至玻璃体腔的21例(23眼)患者,应用玻璃体切割头联合导光纤维机械碎核切除晶状体,观察其疗效.结果脱位晶状体均顺利摘除,用时21~38 min.术中未造成视网膜进一步损伤,术后2眼发生视网膜脱离.术后矫正视力为光感至0.05者3眼,0.06～0.1者4眼,0.2～0.3者9眼,0.3以上者7眼.结论 对于脱位至玻璃体腔的核硬度Ⅲ级及以下的晶状体,应用玻璃体切割头联合导光纤维头机械碎核切除安全有效.     

Single lens to lens duplication: the missing link

Congenital anomalies of the lens include a wide range from lens coloboma to primary aphakia and doubling of lens. There have been few case reports of double lens; the etiology suggested is metaplastic changes in the surface ectoderm that leads to formation of two lens vesicles and hence resulting in double lens. We report a case with bilobed lens, which raises the possibility of explaining the etiology of double lens.     

Some observations on the magnesium metabolism of the rabbit lens

The (Mg) concentration in the rabbit lens is about 3.25 mmol/kg wet wt or 4.7 mM. This level is much greater than that in the bathing aqueous and vitreous humors. The Mg concentration in the peripheral part of this tissue is about four times greater than that in the inner 'nuclear' regions. Exchanges of Mg between the lens and its bathing fluids are very slow; under control conditions the lens appears to be virtually impermeable to Mg. Exposure to metabolic inhibitors, depolarizing concentrations of potassium, ouabain or replacement of Na with Li had little effect on the Mg content of the lens. Incubation of lenses in solutions containing EDTA or following freezing and thawing suggested that much of the Mg is present in a bound form. The ionophore A-23187 increased the permeability of the lens to Mg. Adjustment of the external Mg level in the presence of A-23187 indicated that the internal 'free' Mg concentration was about 3 mM. This result suggests that about 35% of the lenticular magnesium is bound.