Localization of the <Emphasis Type="Italic">PITX2</Emphasis> gene expression in human eye cells in the course of prenatal development

The pattern of the PITX2 gene expression was studied in the cornea, lens, retina, iridocorneal complex (ICC), and eye coats of human fetuses at weeks 9.5–22 of intrauterine development. Using the PCR method, PITX2 expression in all these tissues was revealed already at the earliest stage studied (9.5 weeks), being especially strong in the anterior eye complex (the cornea and lens) and weaker in the retina and sclera. The level of PITX2 expression in all eye tissues slightly decreased by week 15, increased to a high level in the ICC on week 18, and further decreased in all tissues by week 22. Using cDNA derived from the whole eyes of 8-, 9-, 10.5-, and 11-week fetuses, the expression of two PITX2 isoforms specific for eye tissues (A and B) was revealed. By means of in situ hybridization, the PITX2 mRNA was localized in the eye tissues of ectodermal and neuroectodermal origin.     

Structure of the eye of Haideotriton wallacei, a North American troglobitic salamander

The eye of Haideotriton wallacei is more reduced histologically than those of othe troglobitic salamanders. The tiny eye is imbedded in a mass of adipose tissue. No extrinsic eye muscles are present. A rudimentary lens is present in about half of the eyes examined. In two instances the lens is surrounded by a small chamber; most eyes lack a chamber. The retina and iris are relatively undifferentiated. The relatively massive retina lacks rods and cones, an outer plexiform layer and subdivided nuclear layers. A tiny optic nerve runs to the brain.     

STRUCTURE OF THE CEPHALIC TENTACLES OF SOME SPECIES OF PROSOBRANCH LIMPET (PATELLIDAE AND FISSURELLIDAE)

The morphology and ultrastructure of the cephalic tentaclesand eye (optic vesicle) of some patellid and a fissurellid limpetspecies are described. The epithelium of the tentacle bearsciliated cells which have neural connections suggesting a sensoryfunction. In patellid limpets the density of these cells variesbetween species, with the greatest density (18 ciliated tufts.100 µm^–2) being recorded in the territorial limpet,Patella cochlear. The surface of the tentacle of a fissurellidlimpet, Fissurella mutabilis, is papillate, which contrastswith the smooth surface of a patellid tentacle. Ciliated tuftsare borne at the tip of most papillae. Movement of the tentacleis controlled by longitudinal muscle and a radial muscle-collagentissue association, which function as a muscular hydrostat.The eye of a patellid consists of a simple open vesicle anda retina which is comprised of one type of cell. By contrastthe optic vesicle of a fissurellid contains a lens, enclosedby a cornea and a retina which is composed of two types of cell,pigmented and photoreceptive. The ultrastructural features ofthe cells resemble those described for other molluscan eyes. (Received 5 June 1989; accepted 16 August 1989)     

Hydroxyproline concentrations in ocular tissues of Arabian camel (Camelus dromedarius Linn.)

Hydroxyproline (Hyp) concentrations (total, free, peptide-bound and protein-bound) in camel eye tissues were determined. Total Hyp concentration was highest in iris, followed by ciliary body, sclera, cornea, lens and retina; the difference between total Hyp concentration of iris and sclera (P < 0.05) and cornea, lens and retina (P < 0.001) was statistically significant. Cornea had the highest concentration of free Hyp, followed by ciliary body, retina, iris, sclera and lens (P < 0.001). Peptide-bound Hyp concentration was highest in iris, followed by lens, cornea, ciliary body, retina and sclera (P < 0.001). Iris also had the highest concentration of protein-bound Hyp, followed by ciliary body, sclera, cornea, retina and lens; the difference in the protein-bound Hyp concentration between iris and sclera (P < 0.05) and cornea, retina and lens (P < 0.001) was statistically significant. Iris was also found to have the highest concentration of collagen, followed by ciliary body, sclera, cornea, lens and retina; the difference between the collagen concentration of iris and sclera (P < 0.05) and cornea, lens and retina (P < 0.001) was statistically significant. These variations may result from differences in the collagen structure and/or composition in these tissues.     

The lens in focus: a comparison of lens development in Drosophila and vertebrates

The evolution of the eye has been a major subject of study dating back centuries. The advent of molecular genetics offered the surprising finding that morphologically distinct eyes rely on conserved regulatory gene networks for their formation. While many of these advances often stemmed from studies of the compound eye of the fruit fly, Drosophila melanogaster, and later translated to discoveries in vertebrate systems, studies on vertebrate lens development far outnumber those in Drosophila. This may be largely historical, since Spemann and Mangold's paradigm of tissue induction was discovered in the amphibian lens. Recent studies on lens development in Drosophila have begun to define molecular commonalities with the vertebrate lens. Here, we provide an overview of Drosophila lens development, discussing intrinsic and extrinsic factors controlling lens cell specification and differentiation. We then summarize key morphological and molecular events in vertebrate lens development, emphasizing regulatory factors and networks strongly associated with both systems. Finally, we provide a comparative analysis that highlights areas of research that would help further clarify the degree of conservation between the formation of dioptric systems in invertebrates and vertebrates.     

The Sine oculis/Six class family of homeobox genes in jellyfish with and without eyes: development and eye regeneration

The development of visual organs is regulated in Bilateria by a network of genes where members of the Six and Pax gene families play a central role. To investigate the molecular aspects of eye evolution, we analyzed the structure and expression patterns of cognate members of the Six family genes in jellyfish (Cnidaria, Hydrozoa), representatives of a basal, non-bilaterian phylum where complex lens eyes with spherical lens, an epidermal cornea, and a retina appear for the first time in evolution. In the jellyfish Cladonema radiatum, a species with well-developed lens eyes in the tentacle bulbs, Six1/2-Cr and Six3/6-Cr, are expressed in the eye cup. Six4/5-Cr is mainly expressed in the manubrium, the feeding, and sex organ. All three Six genes are expressed in different subsets of epidermal nerve cells, possibly of the RFamide type which are part of a net connecting the different eyes with each other and the effector organs. Furthermore, expression is found in other tissues, notably in the striated muscle. During eye regeneration, expression of Six1/2-Cr and Six3/6-Cr is upregulated, but not of Six4/5-Cr. In Podocoryne carnea, a jellyfish without eyes, Six1/2-Pc and Six3/6-Pc are also expressed in the tentacle bulbs, Six1/2-Pc additionally in the manubrium and striated muscle, and Six3/6-Pc in the mechanosensory nematocytes of the tentacle. The conserved gene structure and expression patterns of all Cladonema Six genes suggest broad conservation of upstream regulatory mechanisms in eye development.     

Dominant inhibition of lens placode formation in mice

The lens in the vertebrate eye has been shown to be critical for proper differentiation of the surrounding ocular tissues including the cornea, iris and ciliary body. In mice, previous investigators have assayed the consequences of molecular ablation of the lens. However, in these studies, lens ablation was initiated (and completed) after the cornea, retina, iris and ciliary body had initiated their differentiation programs thereby precluding analysis of the early role of the lens in fate determination of these tissues. In the present study, we have ablated the lens precursor cells of the surface ectoderm by generation of transgenic mice that express an attenuated version of diphtheria toxin (Tox176) linked to a modified Pax6 promoter that is active in the lens ectodermal precursors. In these mice, lens precursor cells fail to express Sox2, Prox1 and αA-crystallin and die before the formation of a lens placode. The Tox176 mice also showed profound alterations in the corneal differentiation program. The corneal epithelium displayed histological features of the skin, and expressed markers of skin differentiation such as Keratin 1 and 10 instead of Keratin 12, a marker of corneal epithelial differentiation. In the Tox176 mice, in the absence of the lens, extensive folding of the retina was seen. However, differentiation of the major cell types in the retina including the ganglion, amacrine, bipolar and horizontal cells was not affected. Unexpectedly, ectopic placement of the retinal pigmented epithelium was seen between the folds of the retina. Initial specification of the presumptive ciliary body and iris at the anterior margins of the retina was not altered in the Tox176 mice but their subsequent differentiation was blocked. Lacrimal and Harderian glands, which are derived from the Pax6-expressing surface ectodermal precursors, also failed to differentiate. These results suggest that, in mice, specification of the retina, ciliary body and iris occurs at the very outset of eye development and independent of the lens. In addition, our results also suggest that the lens cells of the surface ectoderm may be critical for the proper differentiation of the corneal epithelium.     

A fibrous membrane suspends the multifocal lens in the eyes of lampreys and African lungfishes

The sharpness and thus information content of the retinal image in the eye depends on the optical quality of the lens and its accurate positioning in the eye. Multifocal lenses create well‐focused color images and are present in the eyes of all vertebrate groups studied to date (mammals, reptiles including birds, amphibians, and ray‐finned fishes) and occur even in lampreys, i.e., the most basal vertebrates with well‐developed eyes. Results from photoretinoscopy obtained in this study indicate that the Dipnoi (lungfishes), i.e., the closest piscine relatives to tetrapods, also possess multifocal lenses. Suspension of the lens is complex and sophisticated in teleosts (bony fishes) and tetrapods. We studied lens suspension using light and electron microscopy in one species of lamprey (Lampetra fluviatilis) and two species of African lungfish (Protopterus aethiopicus aethiopicus and Protopterus annectens annectens). A fibrous and highly transparent membrane suspends the lens in both of these phylogenetically widely separated vertebrate groups. The membrane attaches to the lens approximately along the lens equator, from where it extends to the ora retinalis. The material forming the membrane is similar in ultrastructure to microfibrils in the zonule fibers of tetrapods. The membrane, possibly in conjunction with the cornea, iris, and vitreous body, seems suitable for keeping the lens in the correct position for well‐focused imaging. Suspension of the lens by a multitude of zonule fibers in tetrapods may have evolved from a suspensory membrane similar to that in extant African lungfishes, a structure that seems to have appeared first in the lamprey‐like ancestors of allextant vertebrates. J. Morphol. 271:980–989, 2010. © 2010 Wiley‐Liss, Inc.     

Ontogeny of Spectral Transmission in the Eye of the Tropical Damselfish, Dascyllus albisella (Pomacentridae), and Possible Effects on UV Vision

The visual ecology of fishes places changing demands on their visual system during development. Study of changes in the eye can suggest possible changes in behavioral ecology. The spectral transmission of the pre-retinal ocular media controls the wavelength of light that reaches the retina and is a simply measured indication of their potential visual capabilities. Dascyllus albisella is a coral reef planktivore known to have UV-sensitive retinal cone cells. UV vision probably aids in detection of zooplankton. As a juvenile it is very closely associated with branching coral heads or, more rarely, sea anemones. As it matures, it ventures farther from its coral, above the reef, and eventually assumes a more vagile life style, moving farther and more frequently afield. Their eyes contain short-wavelength blocking compounds in the lens, cornea and humors. As they age, both the lens and the cornea accumulate blocking compounds that increase the 50% transmission cutoff of the whole eye from ca. 330nm in 2–3cm juveniles to ca. 360nm in the largest adults. The cornea increases its cutoff wavelength faster than the lens and becomes the primary filter in large adults. The cutoff of the aqueous and vitreous humors combined does not change with size. The slope of the transmission cutoff curve increases with the size of the fish. The increased blocking of UV radiation is likely not an adaptation to protect the eye from short-wavelength induced damage. Instead it probably reduces the image degradation effects of short-wavelength light in the largest eyes and still allows sufficient penetration of UV radiation to permit functional UV vision.     

Transdifferentiation of ocular tissues in larval Xenopus laevis

Transdifferentiation phenomena offer a useful opportunity to study experimentally the mechanisms on which cell phenotypic stability depends. The capacities of vertebrate eye tissues to reprogram cell differentiation are well known in avian and mammalian embryos, and in larval and adult newt. From research into the capacity of anuran eye tissues to reprogram differentiation into a new pathway, considerable data have accumulated concerning the transdifferentiative capacities of eye tissues in larval Xenopus laevis. This work reviews the data concerning the transdifferentiative phenomena of eye tissues in that species and, based on these, aims to establish the extent of our knowledge about the mechanism controlling these processes. In larval Xenopus laevis the outer cornea can regenerate a lens by a lens-transdifferentiation process triggered and substained by a factor(s), probably of a protein nature, produced by the neural retina. In a normal eye phenotypic stability of the outer cornea is guaranteed by the presence of the inner cornea and lens, which prevent the spread of retinal factor(s). The stimulus for lens transdifferentiation of the outer cornea can be supplied by other tissues as well, but this capacity is not widely distributed. The iris and retinal pigmented epithelium can transdifferentiate into neural retina if isolated from the surrounding tissues and implanted in the vitreous chamber. As for lens transdifferentiation of the outer cornea, retinal transdifferentiation of the iris can be stimulated by certain nonocular tissues as well.     

Evaluation of a 345 nm Femtosecond Laser for Corneal Surgery with Respect to Intraocular Radiation Hazard

Purpose

We report our findings from a preclinical safety study designed to assess potential side effects of corneal ultraviolet femtosecond laser treatment on lens and retina.

Methods

Refractive lenticules (-5 dpt) with a diameter of 6 mm were created in the right cornea of eight Dutch Belted rabbits. Radiant exposure was 0.5 J/cm² in two animals and 18 J/cm² in six animals. The presence of lens opacities was assessed prior to and up to six months following laser application using Scheimpflug images (Pentacam, Oculus) and backscatter analysis (Opacity Lensmeter 702, Interzeag). Ganzfeld flash and flicker electroretinogram (ERG) recordings were obtained from both eyes prior to and up to six weeks following laser application. At the study endpoint, retinas were examined by light microscopy.

Results

Independent of energy dose applied, no cataract formation could be observed clinically or with either of the two objective methods used. No changes in ERG recordings over time and no difference between treated and untreated eye were detected. Histologically, retinal morphology was preserved and retinal pigment epithelium as well as photoreceptor inner and outer segments appeared undamaged. Quantitative digital image analysis did not reveal cell loss in inner or outer nuclear layers.

Conclusions

Our analysis confirms theoretical considerations suggesting that ultraviolet femtosecond laser treatment of the cornea is safe for intraocular tissues. Transmitted light including stray light induces no photochemical effects in lens or retina at energy levels much higher than required for the clinical purpose. These conclusions cannot be applied to eyes with pre-existing retinal damage, as these may be more vulnerable to light.     

胭脂鱼眼早期形态发生研究

采用组织学方法观察了胭脂鱼(Myxocyprinus asiaticus) 眼的发生过程, 结果显示: 胭脂鱼眼的发育经历了眼原基形成期、眼囊形成期、视杯形成期、晶体板形成期、晶体囊形成期、角膜原基形成期、角膜上皮形成期、视网膜细胞增殖期、晶状体成熟期、眼色素形成期以及眼成型期等11个时期。视网膜发育最早, 起始于眼原基的形成, 直至眼成型期分化完成, 形成了厚度不一的8层细胞, 由内向外依次为神经纤维层、神经细胞层、内网层、内核层、外网层、外核层、视杆视锥层和色素上皮层, 且发育历时最长, 约264h。晶状体的发育在视网膜之后, 始于晶体板的形成, 于出膜前期成熟, 发育历时最短, 约74h。角膜发育最晚, 始于角膜原基的形成, 出膜1 d分化为透明的成熟角膜, 发育历时约96h。出膜4 d仔鱼眼色素沉积明显, 视网膜各层分化明显, 晶状体内部完全纤维化, 眼的形态结构基本发育完全。     

Cavefish as a model system in evolutionary developmental biology

The Mexican tetra Astyanax mexicanus has many of the favorable attributes that have made the zebrafish a model system in developmental biology. The existence of eyed surface (surface fish) and blind cave (cavefish) dwelling forms in Astyanax also provides an attractive system for studying the evolution of developmental mechanisms. The polarity of evolutionary changes and the environmental conditions leading to the cavefish phenotype are known with certainty, and several different cavefish populations have evolved constructive and regressive changes independently. The constructive changes include enhancement of the feeding apparatus (jaws, taste buds, and teeth) and the mechanosensory system of cranial neuromasts. The homeobox gene Prox 1, which is expressed in the expanded taste buds and cranial neuromasts, is one of the genes involved in the constructive changes in sensory organ development. The regressive changes include loss of pigmentation and eye degeneration. Although adult cavefish lack functional eyes, small eye primordia are formed during embryogenesis, which later arrest in development, degenerate, and sink into the orbit. Apoptosis and lens signaling to other eye parts, such as the cornea, iris, and retina, result in the arrest of eye development and ultimate optic degeneration. Accordingly, an eye with restored cornea, iris, and retinal photoreceptor cells is formed when a surface fish lens is transplanted into a cavefish optic cup, indicating that cavefish optic tissues have conserved the ability to respond to lens signaling. Genetic analysis indicates that multiple genes regulate eye degeneration, and molecular studies suggest that Pax6 may be one of the genes controlling cavefish eye degeneration. Further studies of the Astyanax system will contribute to our understanding of the evolution of developmental mechanisms in vertebrates.     

Ultrastructure of the eye of the amber snail Succinea putris (L.) (Gastropoda, Stylommatophora)]

The structure and some aspects of the development of the eye of Succinea putris were studied with the aid of the electron microscope. The eye is of the closed vesicle type and is composed of retina, cornea, vitreous body, lens and optic nerve. Three different types of cell are to be found in the retina: (1) the small elongated pigment cell with an avoid nucleus, many pigment granulae and short microvilli at the apical end of the cell; (2) the sensory cell type I with a large irregular nucleus, long microvilli, which extend to under the surface of the lens, a large number of light-cored vesicles, 700 A in diameter and the axon; (3) the elongated slender sensory cell type II with many dense cored vesicles, several pigment granulae in the distal region of the cell and short irregular microvilli at the apical end of the cell. This type is few in number. Two results of the study of the embryonic eye are described: the cornea cells differ from those in the adult eye in the nucleus-cytoplasm relation and the optic nerve is smaller than in the adult eye.     

Retina and lens regeneration in anuran amphibians

Anuran amphibians can regenerate the retina through differentiation of stem cells in the ciliary marginal zone and through transdifferentiation of the retinal pigmented epithelium. By contrast, the regeneration of the lens has been demonstrated only in larvae of species belonging to the Xenopus genus, where the lens regenerates through transdifferentiation of the outer cornea. Retinal pigmented epithelium to neural retina and outer cornea to lens transdifferentiation processes are triggered and sustained by signaling molecules belonging to the family of the fibroblast growth factor. Both during retina and lens regeneration there is a re-activation of many of the genes which are activated during development of the eye, even though the spatial and temporal pattern of gene expression is not a simple repetition of that found in development.     

Differential expression of the HMGN family of chromatin proteins during ocular development

The HMGN proteins are a group of non-histone nuclear proteins that associate with the core nucleosome and alter the structure of the chromatin fiber. We investigated the distribution of the three best characterized HMGN family members, HMGN1, HMGN2 and HMGN3 during mouse eye development. HMGN1 protein is evenly distributed in all ocular structures of 10.5 days post-coitum (dpc) mouse embryos however, by 13.5dpc, relatively less HMGN1 is detected in the newly formed lens fiber cells compared to other cell types. In the adult, HMGN1 is detected throughout the retina and lens, although in the cornea, HMGN1 protein is predominately located in the epithelium. HMGN2 is also abundant in all ocular structures of mouse embryos, however, unlike HMGN1, intense immunolabeling is maintained in the lens fiber cells at 13.5dpc. In the adult eye, HMGN2 protein is still found in all lens nuclei while in the cornea, HMGN2 protein is mostly restricted to the epithelium. In contrast, the first detection of HMGN3 in the eye is in the presumptive corneal epithelium and lens fiber cells at 13.5dpc. In the lens, HMGN3 remained lens fiber cell preferred into adulthood. In the cornea, HMGN3 is transiently upregulated in the stroma and endothelium at birth while its expression is restricted to the corneal epithelium in adulthood. In the retina, HMGN3 upregulates around 2 weeks of age and is found at relatively high levels in the inner nuclear and ganglion cell layers of the adult retina. RT-PCR analysis determined that the predominant HMGN3 splice form found in ocular tissues is HMGN3b which lacks the chromatin unfolding domain although HMGN3a mRNA is also detected. These results demonstrate that the HMGN class of chromatin proteins has a dynamic expression pattern in the developing eye.     

The stepwise development of the lamprey visual system and its evolutionary implications

Lampreys, which represent the oldest group of living vertebrates (cyclostomes), show unique eye development. The lamprey larva has only eyespot‐like immature eyes beneath a non‐transparent skin, whereas after metamorphosis, the adult has well‐developed image‐forming camera eyes. To establish a functional visual system, well‐organised visual centres as well as motor components (e.g. trunk muscles for locomotion) and interactions between them are needed. Here we review the available knowledge concerning the structure, function and development of the different parts of the lamprey visual system. The lamprey exhibits stepwise development of the visual system during its life cycle. In prolarvae and early larvae, the ‘primary’ retina does not have horizontal and amacrine cells, but does have photoreceptors, bipolar cells and ganglion cells. At this stage, the optic nerve projects mostly to the pretectum, where the dendrites of neurons in the nucleus of the medial longitudinal fasciculus (nMLF) appear to receive direct visual information and send motor outputs to the neck and trunk muscles. This simple neural circuit may generate negative phototaxis. Through the larval period, the lateral region of the retina grows again to form the ‘secondary’ retina and the topographic retinotectal projection of the optic nerve is formed, and at the same time, the extra‐ocular muscles progressively develop. During metamorphosis, horizontal and amacrine cells differentiate for the first time, and the optic tectum expands and becomes laminated. The adult lamprey then has a sophisticated visual system for image‐forming and visual decision‐making. In the adult lamprey, the thalamic pathway (retina–thalamus–cortex/pallium) also transmits visual stimuli. Because the primary, simple light‐detecting circuit in larval lamprey shares functional and developmental similarities with that of protochordates (amphioxus and tunicates), the visual development of the lamprey provides information regarding the evolutionary transition of the vertebrate visual system from the protochordate‐type to the vertebrate‐type.