Showing papers in "Investigative Ophthalmology & Visual Science in 1969"

Retinal dystrophy in the rat--a pigment epithelial disease.

Abstract: Rod outer segment renewal rate was studied by autoradiographic technique in both the Wistar rat (control) and the Royal College of Surgeons (RCS) dystrophic rat. The dystrophic rat showed normal renewal rate until age 18 days, whereupon further outer segment disc movement slowed and a previously established retrograde degeneration of outer segments progressed. The dystrophic rat differed from the normal in that it showed no evidence of phagocytosis of rod outer segment material by its pigment epithelium. Argument that the primary retinal defect is at the level of the pigment epithelium is presented.

Transplantation and Rejection of Individual Cell Layers of the Cornea

Abstract: Techniques have been developed for the transplantation of allografts of pure rabbit corneal epithelium and of endothelium with Descemet's membrane and only minimal amounts of adherent donor stroma. By appropriately inducing vascularization of the donor graft, the recipient becomes sensitized to and ultimately rejects the pure epithelial graft. The epithelium is rejected as a moving front of infiltrated and dying donor cells, with the rapidly regenerating recipient epithelium effecting immediate repair of the defect. The entire epithelial rejection process takes place in the absence of persisting stromal edema and cloudiness. Sensitization by, and rejection of, pure corneal stromal allografts were also studied. Rejection is characterized by a diffuse band of leukocytic infiltrate which sweeps across the donor tissue, leaving dead keratocytes in its wake. Endothelial allografts also lead to sensitization of the recipient and to graft rejection, again when appropriate vascularization is induced. Like epithelium, the rejection of corneal endothelium is associated with an advancing front of densely infiltrated and dying cells. In this instance, however, repair of the defect by recipient endothelium is so slow that edema and cloudiness of the overlying stroma develop and persist for long periods of time. Endothelial regeneration in the rabbit is associated with substantial recovery of corneal clarity.

Deformation of the globe under high-speed impact: it relation to contusion injuries.

Abstract: D, Enucleated pig eyes in 10 per cent gelatin were submitted to nonperforating injury in order to record and measure the deformations of the eye and explain the mechanism of damage at the vitreous base. High-speed motion pictures and single flash high-speed photographs were used for this purpose. The general theory of the central impact of two bodies was correlated with previous and present experiments. Reconstruction of the motion was based on the constancy of the mass of the globe and on the experimental data obtained. This reconstruction was used to determine local accelerations of the ocular coats, distension of the walls, energetic balance and magnitude of the forces involved. A theory was proposed to explain the damage observed at the vitreous base.

Evaporation rate of water from the precorneal tear film and cornea in the rabbit

Abstract: A technique for the study of evaporation from the precorneal and cornea! surfaces has been developed. Evaporation from the superficial lipid layer (SLL) has been measured to be 10.1 x 10~ 7 Gm.cm.^secr 1 When this lipid layer is removed, evaporation increases around fourfold. Evaporation from the dry epithelial surface occurs at a rate of 1.8 x JO" 7 Gm.cmr^secr 1 After the epithelium is removed, a twentyfold increase in evaporation rate occurs. The specific resistances (u) to evaporation of these layers have been calculated: epithelium, = 82.5 sec./ cm.; SLL, = 12.9 sec/cm.; aqueous tears, < 1 sec/cm.; stroma, < 0 sec/cm. Thus, the superficial lipid layer is effective in retarding evaporation of the precorneal tear film. Its effectiveness compares favorably to that of condensed monolayers of long-chain fatty alcohols on pure water, known to be efficient in retarding evaporation. The epithelium functions as a barrier to water flow and is highly effective in retarding evaporation in the absence of a tear film.

Oxygen supply to the retina from the retinal and choroidal circulations at normal and increased arterial oxygen tensions

Abstract: During oxygen breathing small retinal vessels constrict severely and retinal blood flow drops to less than half the value on air. This paper contains a quantitative explanation of why this occurs based on published figures for the arteriovenous oxygen difference and blood flow in the retinal and choroidal circulations. The choroid has a high blood flow and a low arteriovenous oxygen difference. Once the arterial oxygen tension, paOt, rises to about 270 mm. Hg, the intake of the oxygen extraction from the choroidal blood can be met from dissolved oxygen. When pa0t rises above this level the oxygen tension in the choroidal tissue and venous blood rises in step xoith it because the capacity of reduced hemoglobin to buffer changes in oxygen pressure is lost. At a paO- of 400 mm. Hg, 97 per cent of the retina between the choriocapillaris and the deep retinal capillaries is supplied with oxygen from the choroid compared with 60 per cent on air. At higher values of pa0s there is a delivery of oxygen from the choroid to the deep retinal capillaries and under hyperbaric oxygen almost the whole thickness of retina could be supplied with oxygen from the choroid alone.

The Early Field Defects in Glaucoma

Abstract: the visual field. We cannot rule out glaucoma by testing a predetermined or specific area in the visual field. A complete examination of the visual field is best performed by using both static and kinetic perimetry together. This seems to constitute the best means of modern quantitative perimetry. Scatter of test points can be controlled only by careful attention to numerous details involving physical, pharmacological, physiological, and psychological factors, the \"chaff\" which must be differentiatied from the \"wheat\"—the pathological patterns to be delineated in testing the visual field. The factors causing scatter also influence the reproducibility of a given visual field from one date to another, as do the refractive media, pupil size, mental status, and choice of data points.

Development of the Rat Retina

Abstract: tion of the structures in the anterior segment is well advanced at this time. The anterior chamber is formed and the cornea is covered by a two-layered epithelium and a normal endothelium overlying a thin Descemet's membrane. The anatomical features of the lens are similar to those of the neonatal animal and the posterior mesodermal leaf of the iris has begun to extend forward over the surface of the lens. It is difficult to visualize that transient or prolonged hypoxia at midterm can have brought about the developmental disturbances seen in the anterior segment, as the separation of the lens vesicle from the cornea must have taken place earlier in the gestation period. The circumscribed anterior cortical cataract observed in one eye was complicated by the adherence of a dense portion of the persistent pupillary membrane to the anterior pole of the lens, as is frequently seen in congenital anterior polar cataracts of man. The fetal nucleus was undisturbed, indicating that, as in the human eye, the error of development occurred later in fetal life. It is possible that the hypoxia experimentally induced at midterm delayed the involution or produced shrinkage of the pupillary membrane affecting the structure of the anterior pole of the lens. No attempts can be made to discuss the mechanisms involved in the pathogenesis of the retinal abnormalities. The alteration of hemodynamics produced in the ocular vasculature by the intrauterine surgical procedures cannot be defined and the time course of the development of collateral circulation via the vertebral vessels is unknown. It is probable that the choroidal vasculature was not drastically injured by the experimental procedure. At full term, the undisturbed anatomy of the choroidal vessels correlated well with the over-all integrity of the outer layers of the retina. There remains then a wide area for speculation on the mechanisms responsible for the damage. In this preliminary report it can only be stated that deformities in eyes of infant monkeys subjected to surgical interference with the circulation at midterm resemble congenital anomalies of the human eye.

Electron microscopic study of galactose-induced cataract

Abstract: Cataractous lenses induced by galactose feeding were studied electron microscopically. The early changes were increased reactivity of the epithelium, edema of the lens cells, and intercellular cyst formation in the bow and posterior zones. These changes continued with further feeding of galactose until the lens cells became irreversibly damaged. The reactive epithelial cells formed marked cell proliferations.

A biochemical evaluation of a cataract induced in a high-glucose medium.

Abstract: Rabbit lenses were incubated in lowand high-glucose media in an attempt to evaluate the role of the sorbitol pathway in the production of this sugar cataract. The aldose reductase inhibitor, 3,3-tetramethylene glutaric acid (TMG), was employed to block sorbitol formation. Exposing lenses to high glucose leads to an initial linear increase in sorbitol content and lens water. During the first four days of incubation, lens swelling occurs in response to intracellular sorbitol accumidation. Swelling renders cell membranes more permeable to sodium and potassium. During the first four days in high glucose, the swollen lens is able to compensate for this increased leakiness to sodium and potassium, presumably through increasing cation pump activity. Thus there is no increase in the absolute cation level. However, on or about the fifth day in high glucose, the capacity of this compensatory mechanism is exceeded and abrupt changes in lens cations occur. Lens sodium rises and lens potassium falls; the net result is an increase in total cations. At a somewhat later stage, the imdin space of the lens increases as lens fibers rupture and/or become more permeable to imdin. The addition of TMG to the high-glucose medium practically abolishes sorbitol accumulation; it depresses lens swelling, preserves normal cation balance, and maintains lens clarity and transparency for eight days. This suggests that all of the aforementioned changes are interrelated and also emphasizes the primary role played by aldose reductase in the initiation of the entire sequence of cataractous change.

The electrically evoked response (EER) of the visual system : II. Effect of adaptation and retinitis pigmentosa

Abstract: In an attempt to learn the stimulus site of the EER, the following series of experiments was performed. (1) The effect of dark adaptation on EER and VER was determined. The effect was found to be negligible. (2) The effect of eliciting the electric phosphene on the course of dark adaptation was determined. Under our conditions there was no effect. (3) The effect of ambient light on amplitude of EER and VER was determined. Moderate levels of ambient light 7.0 foot-lamberts abolished the VER but 2 x 10 foot-lamberts decreased the EER only 20 per cent in one subject, less in others. (4) The determination of VER and EER on retinitis pigmentosa patients gave varied results. In some patients neither response could be elicited. In several others a sizeable EER coidd be obtained with our standard stimulus. To obtain a VER of the same subjective brightness a light level ivas required that was higher than for normal subjects. Since in all these instances the variables affecting the VER were not the same as those affecting the EER, it is assumed that the cell of origin is not the same for the tioo phenomena. If the cell of origin of the VER is the photoreceptor, it is probable that the cell of origin of the EER is more central than the photoreceptor.

A difference between rods and cones in the renewal of outer segment protein.

Abstract: The renewal of protein has been studied in the retinal rods and cones of the adult frog by electron microscope autoradiography after injection of radioactive amino acids. In both classes of photoreceptor cells, the synthesis of protein is concentrated in the niyoid zone of the inner segment. Newly formed (radioactive) protein is then displaced past the mitochondria of the ellipsoid zone and reaches the outer segment by flowing through the connecting structure. In rods, the labeled protein accumulates at the base of the outer segment, apparently as a component of newly assembled membranous discs, which are then gradually displaced sclerally. In cones, however, no such concentration of radioactive protein has been observed. On the contrary, protein delivered to the outer segment becomes diffusely distributed throughout that structure. TJuis, in the frog, there is a distinct difference between rods and cones in the process of protein renewal.

The survival and rejection of epithelium in experimental corneal transplants

Abstract: Evidence is presented that the epithelium on a donor corneal allograft is neither sloughed off rapidly in the immediate postoperative period, nor is it even slowly replaced by recipient epithelium in the technically successful corneal transplant. Specific immunologic rejection of the surviving epithelium of a graft may take place long after transplantation, and is characterized by a linear defect consisting of dying epithelial cells and inflammatory cells, stainable by topical methylene blue or fluorescein, which defect migrates slowly across the entire surface of the graft until all donor epithelium has been destroyed.

Changes in the levels of free amino acids and myo-inositol in the galactose-exposed lens.

Abstract: Studies of the effects of galactose on the lens have revealed that marked depressions in the levels of free amino acids and free myo-inositol occur. These changes can be demonstrated by incubating a rabbit lens in a medium containing 30 mM. galactose. However, the lens incubated in galactose but also exposed to tetramethylene glutaric, an aldose reductase inhibitor, shows little dulcitol accumulation, a reduction in lens swelling, and preservation of the levels of free amino acids and myo-inositol at near normal levels. If the galactose-exposed lens is kept from swelling by media with appropriate tonicities, the levels of amino acids and inositol are also maintained near normal. The results suggest that depressed levels of these soluble components in the galactose-exposed lens may be due to osmotic effects caused by the retention of dulcitol. In the development of galactose cataract it appears that these early changes, along with electrolyte disturbances and equatorial opacities, are secondary to the primary event, which is the enzymatic reduction of galactose to dulcitol.

The synthesis of basement membrane by the corneal epithelium in bullous keratopathy

Abstract: With the aid of the electron microscope, the ultrastructural changes associated with bullous keratopathy were studied in corneal specimens from a patient with congenital hereditary corneal dystrophy and from one with congenital glaucoma. Within the subepithelial bullae of both specimens, infoldings of the basal plasma membrane of the basal epithelial cells could be observed to contain basement-membrane-like material accompanied by hemidesmosomes. Morphologically identical membranous infoldings and short segments of basement membrane were found along the basal epithelial surface of rabbit corneas in which basement membrane regeneration had been induced by superficial keratectomy. On the basis of these ultrastructural similarities, it is therefore suggested that the formation of subepithelial bullae with the concomitant interruption of the basement membrane induces the corneal epithelium to attempt restoration of the integrity of this layer by the synthesis and deposition of new basement membrane material.

The visual field defect and ocular pressure level in open angle glaucoma.

Abstract: on Claucoma, Josiah Macy, Jr., Foundation, 1960. 4. Becker, B.: Intraocular pressure response to topical corticosteroids, INVEST. OPHTH. 4: 198, 1965. 5. Harrington, D. O.: The pathogenesis of the glaucoma field, Am. J. Ophth. 47:(part 2) : 177, 1959. 6. Drance, S., Wheeler, C, and Pattulo, M.: Uniocular open-angle glaucoma, Am. J. Ophth. 65: 891, 1968. 7. Dubois-Poulsen, A., and Magis, Cl.: Is the Bjerrum scotoma extraocular in origin? XVIII Concilium Ophth. 2: 1136, 1954. 8. Hoyt, W. F.: Anatomic considerations of arcuate scotomas associated with lesions of the optic nerve and chiasm, Bull. Johns Hopkins Hosp. 3:57, 1962. 9. Kearns, T. P., and Rucker, C. W.: Arcuate defects in the visual fields due to chromophobe adenoma of the pituitary gland, Am. J. Ophth. 45:505, 1958. 10. Lansche, R. K., and Rucker, C. W.: Progression of defects in visual fields produced by hyaline bodies in optic discs, Arch. Ophth. 58: 115, 1957. 11. Petersen, H. P.: Cottoid bodies with defects in field of vision, Acta ophth. 35: 243, 1957. 12. Ourgaud, A. F., and Etienne, R.: L'exploration fonctionnelle de l'oeil glaucomateux, Paris, 1961, Masson et Cie., Vol. II, pp. 13811382. 13. Schmidt, T.: Perimetrie relativer Skotome, Ophthalmologica 129: 303, 1955. 14. Enoksson, P.: Perimetry in Neuro-ophthalmological Diagnosis, Acta Ophth., Suppl. 82: 11-14, 1965. 15. Francois, J., Verriest, J., Neetens, A., DeRouck, A., and Hanssens, M.: Pseudo-papillitis vascularies, Ann. Oculist 195: 830, 1962.

Lens development. IV. Size, shape, and orientation.

Abstract: The right lenses were removed from a group of chick embryos at five days of incubation. Each lens was replaced by two lenses from donors of the same age. The donor lenses were implanted so that their equatorial planes lay at right angles to the equatorial plane of the host lens which they replaced. These cases were studied at 14 days of incubation. The volume of such lens pairs became regulated to correspond with that of a single 14-day-old lens. Each lens of an implanted pair assumed the shape of half of a normal 14 day lens bisected by a plane including its axis. Thus, the combined shape of a lens pair came to match that of a single 14 day lens. The lens pairs became internally reorganized: (1) lens epithelial cells which, at the time of implantation, had lain anterior to the plane defined by the edge of the eye cup continued to divide, and spread out to cover those exposed surfaces of the lens pair which lay toward the cornea; (2) those epithelial cells which were positioned toward the vitreous body enlarged and elongated to form lens fibers; (3) as a consequence of these events a new equatorial zone appeared which girdled the lens pair along the line of its contact with the cup margin; (4) in this fashion the orientation of the lens pair was readjusted in a manner appropriate for the host eye. These experiments demonstrate the existence of mechanisms which control the size, shape, and orientation of the developing lens. It is suggested that these mechanisms include an influence from the limbic mesenchyme which promotes cell elongation and cell packing, and a neural retinal influence which promotes enlargement of the lens cells as they form lens fibers. .his study deals with the mechanisms which control the size and shape of the embryonic lens, and which regulate its orientation in the growing eye. The size of the developing lens normally increases at a rate which is compatible with the dimensions of the developing eye. 1 ' 3 Harrison, 4 using early stages in amphibian development, demonstrated that this coordinated growth is brought about by a mutual adjustment of the growth rates of the lens and the eye wall. Our

Brain pathology following fetal vascular occlusion: an experimental study.

Abstract: .he Laboratory of Perinatal Physiology received a remarkable monkey brain specimen in 1964 from a group at the Oregon Regional Primate Research Center who had been investigating the effects of chronic anemia on the in utero development of the monkey fetus.* These investigators had ligated the common carotid artery and the jugular vein bilaterally in the neck of a monkey fetus at 84 days of gestational age during the cannulation of these vessels for the recording of fetal blood pressures and the withdrawal of fetal blood samples. Over many hours blood was withdrawn from this fetus until its hematocrit had dropped from 42 per cent to a low of 18 per cent. The fetus was returned to the uterus and sustained there until its spontaneous vaginal delivery at an estimated gestational age of 163 days—a term infant. Despite its fully developed appearance, the infant was stillborn. However, it

Recurrence of herpes simplex virus in rabbit eyes: Results of a three-year study

Abstract: Spontaneous reactivation of herpes simplex virus in rabbit ocular tissue was found on 112 occasions in 50 rabbits for up to 3 years after the primary eye infection. To detect these spontaneous reappearances of virus, cultures for herpes simplex virus were obtained 5 or 6 clays a week from the cul-de-sac of rabbit eyes for various periods up to 3 years. Keratitis was also intermittently observed but 72 per cent of the viral reactivations occurred without coincidental corneal disease. Once the rabbit eye is infected with herpes simplex virus a chronic inapparent infection ensues which probably persists for the life of the animal.

Mitotic activity in the cortical vitreous cells (hyalocytes) after photocoagulation.

Abstract: After photocoagulation of the rabbit retina wound healing occurs with a marked increase inmitoses not only in choroid, pigment epithelium, and retina, where mainly Midler cells areproliferating, but also in the cortical vitreous cells, the hyalocytes. The rate of mitosis in thehyalocytes ivas investigated by administration of systemic colchicine. The rate of mitosis ishighest around the third to the fifth day post photocoagulation. In localized areas near theregion of photocoagulation and in more diffuse areas in the zonular region corresponding tothe equatorial band of coagulation the rate of mitosis reaches values of up to 100 mitosesper 1,000 cells, when colchicine is in effect for four hours. This is at least five or more timeshigher than in control eyes. The rate of mitosis is high enough to explain, in large part, theincrease in the cell population in the vitreous. The possible relationship between proliferationof hyalocytes after photocoagulation and epiretinal fibroplasia and massive preretinal retractionis discussed.Key words: Cortical vitreous cells (hyalocytes), complications following photocoagulation,epiretinal fibroplasia, massive preretinal retraction, cytology, histology, photocoagulation,wound healing, mitosis, hyalocytes, choroid, retinal pigment epithelium, retinal Mueller cell,ciliary body epithelium, colchicine, pharmacodynamics, histopathology, time factors, rabbits.From the Department of Ophthalmology, Wash-ington University School of Medicine, St. Louis,Mo. 63110.This investigation was conducted under the FightFor Sight Postdoctoral Research Fellowship ofFight For Sight, Inc., New York City, No.F-209, and was supported in part by NationalInstitutes of Health Grant No. NB 10789 andB 621.Presented in part at the meeting of the Associa-tion for Research in Ophthalmology, Tampa,Fla., April 20, 1969.Reprint requests to: Dr. Gloor, Universitats-Augenklinik, Bern, Switzerland.Manuscript submitted May 2, 1969; manuscriptaccepted June 23, 1969.

Atypical mitochondria in the ellipsoid of the photoreceptor cells of vertebrate retinas.

Abstract: The fine structure of ellipsoids in a number of vertebrate retinas was studied in material prepared with various fixatives Several atypical ellipsoidal mitochondria were found in ellipsoids of certain animals A peculiar configuration of the internal mitochondrial membranes caused by fusion of the outer surfaces of adjacent cristae was found in the lamprey retina Intramitochondrial glycogen granules and granular or filamentous intracristal inclusions were observed in the toad and giant salamander, respectively In photoreceptor cells of the gecko, carp, and snake, the ellipsoid was particularly differentiated, containing modified mitochondria The possible functional significance of such differentiated ellipsoids is discussed briefly with respect to the oil droplets

The human electroretinogram and occipital potential in response to focal illumination of the retina.

Abstract: Electrical responses to light stimuli of 1° angular subtense were recorded from the eye (electroretinogram, ERG) and from the occiput (visual evoked response, VER) in normal subjects and in patients with visual field defects Suitable combinations of stimulus and background intensities were able to produce focal retinal stimulation, evidenced by absence of response to blind spot stimulation and by presence of a clear response with foveal stimulation At a constant level of background light the range of stimulus intensity necessary to effect focal stimulation was much more critical in ERG (1 log unit) than in VER (4 log units) With these parameters, the distribution of VER amplitude on the horizontal meridian of the visual field showed augmentation at the macular area of the retina in the photopic and scotopic state When the stimulus was moved from the center to the periphery along the horizontal meridian, the b-wave of the ERG diminished in most cases more greatly than the a-wave, and was reduced to a prolonged negative wave at the periphery Under these conditions, combined recording of ERG and VER was found to be significant in fudging whether field defects resulted from local disorders of the retina or from lesions higher in the visual system

Regulation of ocular morphogenesis.

Abstract: on Lens Differentiation, 1964, Oak Ridge National Laboratory (abstr.). 29. Rudnick, D., and Waelsch, H.: Development of glutamotransferase and glutamine synthetase in the nervous system of the chick, J. Exper. Zool. 129: 309, 1955. 30. Rudnick, D.: Glutamotransferase and histogenesis in the transplanted chick retina, J. Exper. Zool. 142: 643, 1959. 31. Scott, R. B., and Bell, E.: Protein synthesis during development: control through messenger RNA, Science 145: 711, 1964. 32. Spiro, D., and Hagopian, M.: On the assemblage of myofibrils, in Brehme Warren, K., editor: Formation and fate of cell organelles, New York, 1967, Academic Press, Inc., p. 71. 33. Stewart, J. A., and Papaconstantinou, J.: Stabilization of mRNA templates in bovine lens epithelial cells, J. Molec. Biol. 29: 357, 1967. 34. Stockdale, F. E., and Holtzer, H.: DNA synthesis and myogenesis, Exper. Cell Res. 24: 508, 1961. 35. Stone, L. S.: Further experiments on lens regeneration in eyes of the adult newt Triturus v. viridescens, Anat. Rec. 120: 599, 1954. 36. Tiedemann, H.: The molecular basis of differentiation in early development of amphibian embryos, in Moscona, A. A., and Monroy, A., editors: Current topics in developmental biology, New York, 1966, Academic Press, Inc., vol. 1, p. 85. 37. Traub, P., and Nomura, M.: Structure and function of E. coli ribosomes. V. Reconstitution of functionally active 30S ribosomal particles from RNA and proteins, Proc. Nat. Acad. Sc. 59: 777, 1968. 38. Wolff, G.: Entwickelungsphysiologische Studien. I. Die Regeneration der Urodelenlinse, Roux' Arch. Entw. Mech. Org. 1: 380, 1895. 39. Yamada, T.: Control of tissue specificity: The pattern of cellular synthetic activities in tissue transformation, Am. Zool. 6: 21, 1966. 40. Yamada, T.: Cellular and subcellular events in Wolffian lens regeneration, in Moscona, A. A., and Monroy, A., editors: Current topics in developmental biology, New York, 1967, Academic Press, Inc., vol. 2, p. 247.

Characteristics of Cultured Lens Epithelium

Abstract: A number of lines of rabbit lens epithelium have been groion in large-scale continuous tissue culture for periods of 1 to 2 years. The cells exhibit a marked degree of contact inhibition on the monolayer, suggesting that this phenomenon may play a role in the regulation of cell division in vivo. The availability of large numbers of homogeneous cells has permitted determination of the life cycle of such populations. Some ultrastructural and biochemical characteristics of these cells are presented.

The ability to distinguish which eye was stimulated by light

Abstract: The ability to distinguish which eye has been stimulated by light has been studied in normal and strabismic observers. This response characteristic is not uniformly present in the population, and skill at the task varies markedly among individuals. Scores range from high positive to chance. It is clear that the capability is greatest in the central retina, but not limited to that region. The nature of the sensation experienced by observers is quite unique. The prevalence and inheritance of this response attribute is but one of several interesting questions which need to be studied further.

Experimental chlorpromazine cataracts.

Abstract: Chronic ingestion of large doses of chlorpromazine (CPZ) by human beings has been associated with the production of corneal and lens opacities, and less frequently with chorioretinal pigmentation, and a peculiar purplish coloration of exposed skin and conjunctiva. When guinea pigs were fed large doses of CPZ and exposed to ultraviolet light, lens opacities were consistently produced that resemble those in human patients on chronic high doses of CPZ. They developed in albino and pigmented animals. A progressive increasing deposition of CPZ with increased treatment was demonstrated in the lens and other tissues of treated guinea pigs, and occurred in albino and pigmented animals. The respiratory metabolism of lens epithelium of CPZ-treated animals teas reduced by a statistically significant amount in this study, xohen compared to control values. Sodium succinate was shown to stimidate respiration in CPZtreated, but not control, lens epithelium (both exposed to glucose substrate). It appears that CPZ alters respiratory mechanisms by effecting a metabolic block at some site preceding succinate. On the basis of this study, the CPZ cataract has no apparent relation to melaniti. It may represent foci of denatured protein resulting from the interaction of light with the drug, a photosensitizing agent, and lens protein, or possibly deposits of drug within the lens.