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The relative potency of alpha-adrenoceptor agonists and the dissociation constants of competitive antagonists were studied to characterize the post-junctional alpha-adrenoceptor of the human iris dilator muscle. The data obtained from human iris dilator tissue was compared to that from rabbit. The iris dilator muscle was mounted in an organ bath and tension changes were recorded. (-)-Norepinephrine, (-)-phenylephrine (PE), oxymetazoline and p-aminoclonidine caused contractile responses in albino rabbit, pigmented rabbit and human iris dilator muscle in a concentration-dependent manner. The imidazoline molecules were partial agonists. In rabbit iris dilator, desensitization occurred to repeated oxymetazoline application at an interval of 1 h but recovery to the agonist activity was complete in about 3 h. Exposure to cocaine (10 mumol/l), hydrocortisone (100 mumol/l) and U-0521, a catechol-O-methyltransferase inhibitor (100 mumol/l), significantly potentiated the response to norepinephrine by 92-, 32- and 7 fold in iris dilator tissue of albino rabbit, pigmented rabbit and human, respectively. After block of "uptake1" and "uptake2", the EC50 values of norepinephrine in the albino rabbit, pigmented rabbit and human iris dilator did not differ and ranged from 99 to 195 nmol/l. Small but significant potentiation by uptake blockers was also observed in the responses to PE in the albino rabbit or pigmented rabbit iris dilator. The average maximum tension induced by 100 mumol/l PE was 96 +/- 11 mg (n = 10), 197 +/- 11 mg (n = 11), 45 +/- 5 mg (n = 27) in albino rabbit, pigmented rabbit and human iris dilator, respectively. In human iris dilator, the responses to PE were competitively antagonized by prazosin, 5-methylurapidil and phentolamine with apparent pKB values of 7.3, 6.6 and 7.5, respectively. The pKB values of the prazosin-PE interaction in iris dilator of albino and pigmented rabbit were 8.6 and 6.4, respectively. These results suggest that the post-junctional alpha-adrenoceptors in iris dilator may be similar to that in pigmented rabbit iris. The alpha-adrenoceptor of the human or pigmented rabbit iris dilator may be characterized as alpha 1L-adrenoceptor subtype. The alpha-adrenoceptor of albino rabbit iris dilator appears to be a high affinity subtype. Furthermore, albino rabbit may not be the best strain for the drug research which is relevant to human ocular therapeutics.
The material basis of this investigation consists of empirical findings and colour photographs of the irises of 200 pairs of twins and 100 control pairs. For the morphological investigation first-born twins and control persons are combined to constitute a comparative group of 400 non-related testees. Research by means of the iris microscope and the evaluation of standardized iris photographs led to the development of a catalogue of features which describes 10 iris characteristics for the iris colour and 20 for the iris structure. For each feature different degrees of markedness are defined and their frequency is determined. Similarly, intraindividual right/left and sex differences as well as age-dependencies and the relation between the features are examined. The setting-up of features includes outlining an iris-colour class system in order to render a better and more practicable determination of eye colour possible. As a substitute for Martin/Schulz's table of eye-colour, which describes only eye-colour phenomena, 4 iris-colour classes are set up whose main criterion of classification is the quantity of pigment. When we consider the testees of all age classes, sex differences have no statistical relevance as for iris colour. Only in the case of male testees may an intensive decrease of blue and brown iris colour in favour of combination colours (yellow pigment colours in particular) be observed during the phase of puberty. Therefore, the brightening postulated in the relevant literature can be confirmed. With regard to female testees, in contrast, pigment shifting is of no statistical relevance. After a slight brightening the irises numerically re-darken at the adult-stage to the initial child level, i.e. they become "dark again" rather than just become "darker". Within the iris structure only the characteristics of the anterior stroma leaf show sex differences. They are, however, only weakly marked and can be described merely as a trend. Over the whole range of the age classes, there are no outstanding structural differences. The different iris characteristics concerning iris colour stand in a significant relation to each other. When we consider the statistically relevant relations between structural features, it becomes clear that particularly reduced and particularly intact iris characteristics correlate. Thus, we can distinguish between an intact type of iris and a reduced one. Three quarters of the testees, however, combine reduced and intact properties with medium degrees of markedness.(ABSTRACT TRUNCATED AT 400 WORDS)
PURPOSE: Local treatment of uveal melanoma by radiotherapy involves the use of brachytherapy with radioactive plaques attached to the sclera, or proton irradiation. Both treatments induce growth arrest within the tumour and its slow involution over several years. Although ocular retention rates are excellent, regrowth of tumours due to resistance and neovascular glaucoma leads to enucleation of up to 10% of affected eyes. Proton irradiation involves part of the iris in most cases and we noticed that neovascularisation only occurred in the part of the iris that was not irradiated. We therefore conducted this study to determine the relationship between the development of iris neovascularisation and iris irradiation. METHODS: A total of 21 enucleation specimens from patients who had previously had proton irradiation were collected from the files of the Department of Pathology, Moorfields Eye Hospital during the 5-year period from 1994 to 1999. Sections of these eyes were assessed for VEGF-A, bFGF, and von Willebrand Factor (vWF) by immunohistochemistry. Ophthalmic notes and radiotherapy records were reviewed to assess the extent of iris irradiation. RESULTS: In all, 11 cases showed clinical evidence of iris neovascularisation and were selected for further study. Three of these eyes also showed clinical evidence of regrowth of the tumour. Histological evidence of iris neovascularization was noted in all 11 of the eyes examined, and was only present in the nonirradiated side of the iris in 8/11 eyes. NVI was present on both sides of the iris in three cases, but was less severe in the irradiated part. Expression of VEGF-A was at most weak within the tumour, but was present in the detached retina and in the epithelium of both ciliary body and iris. Some bFGF staining was noted around vessels in the iris stroma. CONCLUSIONS: Our results suggest that irradiation leads to iris atrophy, and that atrophic, irradiated iris is resistant to the development of neovascularisation.
BACKGROUND: Iris cysts in children are uncommon and there is relatively little information on their classification, incidence, and management. METHODS: The records of all children under age 20 years who were diagnosed with iris cyst were reviewed and the types and incidence of iris cysts of childhood determined. Based on these observations recommendations were made regarding management of iris cysts in children. RESULTS: Of 57 iris cysts in children, 53 were primary and four were secondary. There were 44 primary cysts of the iris pigment epithelium, 34 of which were of the peripheral or iridociliary type, accounting for 59% of all childhood iris cysts. It was most commonly diagnosed in the teenage years, more common in girls (68%), was not recognised in infancy, remained stationary or regressed, and required no treatment. The five mid-zonal pigment epithelial cysts were diagnosed at a mean age of 14 years, were more common in boys (83%), remained stationary, and required no treatment. The pupillary type of pigment epithelial cyst was generally recognised in infancy and, despite involvement of the pupillary aperture, also required no treatment. There were nine cases of primary iris stromal cysts, accounting for 16% of all childhood iris cysts. This cyst was usually diagnosed in infancy, was generally progressive, and required treatment in eight of the nine cases, usually by aspiration and cryotherapy or surgical resection. Among the secondary iris cysts, two were post-traumatic epithelial ingrowth cysts and two were tumour induced cysts, one arising from an intraocular lacrimal gland choristoma and one adjacent to a peripheral iris naevus. CONCLUSIONS: Most iris cysts of childhood are primary pigment epithelial cysts and require no treatment. However, the iris stromal cyst, usually recognised in infancy, is generally an aggressive lesion that requires treatment by aspiration or surgical excision.
The pancreaticoduodenal and portal venous blood flows were recorded electromagnetically in anaesthetized dogs. Blood glucose and IRI were measured in the arterial, portal, and peripheral venous as well as in the intestinal venous blood. By a mathematical model the actual net IRI output of the whole pancreas was estimated. Under basal conditions it is 10.2 +/- 2.4 mU/min (n = 30; 26 kg mean body wt.). After i.v. glucose injection, IRI output is rapidly enhanced. The biphasic nature of this reaction was unequivocally demonstrated by consideration of the ratio IRI output : blood glucose. Pancreaticoduodenal blood flow increases transiently in relation to the increased blood glucose concentration. The IRI secretion rate is well correlated with the blood glucose concentration and to the amounts of glucose or of blood reaching the whole pancreas. It is also correlated with the portal IRI Concentration. The overall peripheral venous or arterial IRI concentrations are correlated with the IRI secretion rate, but not in all individual experiments. The different phases of IRI output (basal rate, stimulated output 1-10 min and 10-60 min) show no influence on each other, nor are they correlated with the peripheral IRI concentration area. Basal IRI output is negatively correlated with the glucose assimilation constants. These constants or the peripheral BG areas, however, are independent of the stimulated IRI output rate. However, both the assimilation constants and the peripheral BG areas are related to the peripheral IRI concentration areas. Hepatic uptake of insulin and dynamics of pancreatic blood flow seem to contribute considerably to the estimated correlation pattern.
Eukaryotic genomes can usurp enzymatic functions encoded by mobile elements for their own use. A particularly interesting kind of acquisition involves the domestication of retroviral envelope genes, which confer infectious membrane-fusion ability to retroviruses. So far, these examples have been limited to vertebrate genomes, including primates where the domesticated envelope is under purifying selection to assist placental function. Here, we show that in Drosophila genomes, a previously unannotated gene (CG4715, renamed Iris) was domesticated from a novel, active Kanga lineage of insect retroviruses at least 25 million years ago, and has since been maintained as a host gene that is expressed in all adult tissues. Iris and the envelope genes from Kanga retroviruses are homologous to those found in insect baculoviruses and gypsy and roo insect retroviruses. Two separate envelope domestications from the Kanga and roo retroviruses have taken place, in fruit fly and mosquito genomes, respectively. Whereas retroviral envelopes are proteolytically cleaved into the ligand-interaction and membrane-fusion domains, Iris appears to lack this cleavage site. In the takahashii/suzukii species groups of Drosophila, we find that Iris has tandemly duplicated to give rise to two genes (Iris-A and Iris-B). Iris-B has significantly diverged from the Iris-A lineage, primarily because of the "invention" of an intron de novo in what was previously exonic sequence. Unlike domesticated retroviral envelope genes in mammals, we find that Iris has been subject to strong positive selection between Drosophila species. The rapid, adaptive evolution of Iris is sufficient to unambiguously distinguish the phylogenies of three closely related sibling species of Drosophila (D. simulans, D. sechellia, and D. mauritiana), a discriminative power previously described only for a putative "speciation gene." Iris represents the first instance of a retroviral envelope-derived host gene outside vertebrates. It is also the first example of a retroviral envelope gene that has been found to be subject to positive selection following its domestication. The unusual selective pressures acting on Iris suggest that it is an active participant in an ongoing genetic conflict. We propose a model in which Iris has "switched sides," having been recruited by host genomes to combat baculoviruses and retroviruses, which employ homologous envelope genes to mediate infection.
PURPOSE: To prospectively determine the incidence of a latanoprost-induced increase in iris pigmentation in Japanese brown iris eyes by identifying changes in iris pigmentation on a series of iris color photographs. METHODS: In a cohort study, we prospectively and consecutively enrolled 104 patients (104 eyes) with primary open-angle glaucoma or normal-tension glaucoma who began treatment with latanoprost eye drops for the first time. None of the enrolled patients had a history of previous intraocular surgery or laser surgery. Patients comprised 51 men and 53 women. Their ages ranged from 23 to 80 years (mean +/- SD, 63.8 +/- 10.4 years). Before and every 3 months after starting latanoprost treatment, iris photographs were taken using a slit-lamp biomicroscope with an attached camera. To identify an increase in iris pigmentation, seven glaucoma specialists independently read the series of photographs. If five of the seven observers agreed that iris pigmentation had increased, we determined that the iris pigmentation had increased from the time the previous photograph was taken. Ten normal volunteers served as controls, and photographs of their eyes were used in the evaluation of iris pigmentation. The Kaplan-Meier life table analysis was adopted to evaluate the incidence of increase in iris pigmentation during treatment with latanoprost. RESULTS: The Kaplan-Meier life table analysis indicated that the incidence of increased iris pigmentation at 3, 6, 9, 12, and 15 months after the start of latanoprost treatment was 16.3%, 34.2%, 49.5%, 58.2%, and 58.2%, respectively. CONCLUSIONS: Latanoprost instillation for at least 1 year induced increased iris pigmentation in approximately 50% of the treated Japanese eyes, which is a considerably higher percentage than that reported in Caucasians.
BACKGROUND: Metastatic cancer of the iris is rare. We report a case of breast carcinoma which metastasized to the iris and a review of the literature. METHOD: A 60-year-old woman with a history of breast carcinoma presented with lesions of the iris 5 years after diagnosis and tumor excision. In addition to slit-lamp examination including gonioscopy, ultrasound biomicroscopy, positron-emission tomography and fluorescein angiography of the iris were used for diagnosis. Furthermore, the literature was searched using the medline database. RESULTS: The iris metastasis exhibited multiple whitish to pink nodules on the inferior half of the iris and infiltration of the chamber angle. The main tumor mass was prominent and highly vascularized. Best corrected visual acuity was 20/40 and the intraocular pressure was 7 mmHg. Ultrasound biomicroscopy showed lobular masses characterized by mid to low reflectivity and there was no distinct border to the surrounding tissue. Fluorescein angiography of the iris showed tumor vessels with dye leakage. The positron-emission tomography displayed metastatic lesions to the liver, lung, bones and lymph nodules in addition to the lesion of the iris. The review of the literature revealed that breast carcinoma leads to choroidal metastases in 5% of cases and iris metastases are even rarer. In twothirds of these cases the lesions form unilateral whitish to red clumps at the horizontal meridian and in the inferior quadrants of the iris. The preferred treatment is chemotherapy and/or radiation therapy. CONCLUSIONS: Breast carcinoma is rarely associated with iris metastasis. Positron-emission tomography is a sensitive diagnostic tool to identify metastatic lesions and is a useful method for planning therapeutic approaches. Radiation therapy, argon laser treatment and block excision are therapeutic options with an isolated metastasis of the iris.
OBJECTIVE: To identify risk factors that predict distant metastases of iris malignant melanoma. DESIGN: Retrospective case series. PARTICIPANTS: The participants included 169 consecutive patients with microscopically confirmed iris malignant melanoma managed on the Oncology Service at Wills Eye Hospital between 1974 and 1999. MAIN OUTCOME MEASURES: The main outcome measure was the development of distant tumor metastasis. Cox proportional regression models were used to calculate the risk of eventual metastatic spread. RESULTS: Of 1054 patients referred with suspicious iris melanocytic tumors (rule out malignant melanoma) over a 25-year period, 169 patients (16%) had microscopically proven iris melanoma, and the remainder (84%) had clinically diagnosed iris nevus. Of the patients with iris melanoma, the mean age at the time of diagnosis was 43 years (median, 45 years; range, 1-90 years). All patients were Caucasian. The mean tumor base was 6 mm (median, 5 mm; range, 1-17 mm), and mean tumor thickness was 2 mm (median, 2 mm; range, 1-4 mm). The mean number of clock hours of tumor involvement in the iris was four, tumor seeding on the iris was four, and tumor seeding into the anterior chamber angle was four. Extraocular extension was present in 10 eyes (6%). The tumor management consisted of local resection (iridectomy, iridocyclectomy, or iridocyclogoniectomy) in 102 patients (60%), enucleation in 51 (30%), plaque radiotherapy in 9 (5%), and observation in 7 patients (4%). Metastasis developed in nine patients (5%). Using Kaplan-Meier life table analysis, metastasis was found in 3% of patients at 5 years, 5% at 10 years, and 10% at 20 years. The clinical factors at initial evaluation predictive of eventual metastasis from iris melanoma included increasing age at diagnosis (P = 0.03), elevated intraocular pressure (P = 0.03), posterior tumor margin at angle or iris root (versus midzone) (P = 0.02), extraocular extension (P: = 0.02), and prior surgical treatment of the tumor elsewhere before referral (versus observation) (P = 0.006). The method of management (resection, radiotherapy, or enucleation) did not have an impact on metastasis. CONCLUSIONS: Microscopically confirmed iris melanoma demonstrates distant metastasis in 5% of patients at 10 years follow-up. Metastases are more likely to develop in those patients who are older and show tumor features of iris root/angle location with elevated intraocular pressure and extraocular extension.
PURPOSE: To evaluate the effects of topical carteolol or timolol on tissue circulation in the iris and posterior choroid. METHODS: After a topical instillation of 20 microl of 2% carteolol, 0.5% timolol, or physiological saline (for control) into one eye, and physiological saline into the other eye of pentobarbital-anesthetized Dutch pigmented rabbits, normalized blur value; a quantitative index of tissue blood velocity in the iris (NB(iris)) and posterior choroid (NB(cho)) was obtained using the laser-speckle method. Intraocular pressure (IOP), blood pressure and pulse rate were serially monitored for 2 hours after instillation. Using separate groups of rabbits, NB(iris) and IOP were measured before and after 20-day twice-daily unilateral treatment of carteolol or timolol. RESULTS: After a single instillation of carteolol, NB(iris) was significantly greater only in the treated eyes than control eyes (P = 0.0050, repeated measures two-way ANOVA), while NB(cho) showed no significant change. IOP in the treated eyes significantly reduced (P = 0.0005). Bilateral reductions of tissue vascular resistance in the iris were found after carteolol instillation (P = 0.0183 approximately 0.0322). After timolol instillation, serial changes in NB(iris) and NB(cho) in the treated eyes were significantly different from those in control eyes (P = 0.0129, 0.0031), while there were no significant differences at any of time points (Mann-Whitney test); IOP in both eyes was significantly reduced (P = 0.0096 approximately 0.0005); tissue vascular resistance in the iris and posterior choroid showed no significant changes. After 20-day treatment, NB(iris) in the both eyes of carteolol-treated rabbits significantly increased from the baseline (P = 0.0280, 0.0425, Wilcoxon signed rank test) and NB(iris) in timolol-treated eyes significantly decreased (P = 0.0280). CONCLUSIONS: A single instillation of topical carteolol significantly increased the iris tissue blood velocity in the treated eye and reduced the tissue vascular resistance in both eyes. Topical timolol tended to decrease tissue blood velocity in the iris and choroid of the treated eye, but showed no significant effects on tissue vascular resistance in the both tissues.
The experiments were designed to study the well-known pigment-dependent mydriatic effect of atropine in the eye. In vitro, relative to the accumulation of 3H-atropine by the nonpigmented rabbit iris, the pigmented iris accumulated high amounts of the drug. A nonpigmented tissue, stomch fundus strip, obtained from either albino or nonalbino animals, accumulated relatively low amounts of 3H-atropine. On repeated washings, the accumulated drug from the nonpigmented tissues was rapidly lost, T 1/2 of 14 minutes, while that accumulated by the pigmented iris was retained much longer. Although in vitro aqueous humor from serum-atropinesterase positive rabbits rapidly degraded atropine, extracts from irides of the same type of rabbit gave a single peak radioactivity, with Rf identical to the authentic atropine sulfate. The accumulation of 3H-atropine by pigmented human iris or pigment epithelium was similar to that observed for the pigmented rabbit iris. pA2 values of atropine from nonpigmented iris and from fundus strips varied between 8.58 and 8.88 with slope values close to 1. The pA2 value of atropine in pigmented iris was 8.82; at higher concentrations, atropine was less effective compared to the nonpigmented iris. In the pigmented iris, the lesser effectiveness of the drug at high concentration could be explained on the basis of accumulation of the drug by the pigment cell and its constituents. Thus, the free concentration of the drug in the vicinity of the muscarinic receptor will fall. The lesser concentration will give weaker muscarinic blockade in the pigmented iris. On repeated washing, the atropine blockade of the nonpigmented iris could be easily washed out while that in the pigmented iris was retained. In vivo, the relative T 1/2 for the duration of atropine mydriasis in rabbits were: albino atropinesterase-positive, 3.8 hours; nonalbino atropinesterase-positive, 12.4 hours; albino atropinesterase-negative is greater than or equal to 96 hours. Only the latter T 1/2 for the duration of atropine mydriasis is quite clear. The small magnitude of the mydriatic effect in humans is explained by the loss of free drug to the pigment cells and their constituents. The longer duration of mydriatic effect in the heavily pigmented eye is explained on the basis of slow release of the accumulated drug onto the muscarinic receptor.
BACKGROUND: Some patients with HIV/tuberculosis (TB) coinfection who are on anti-TB treatment and highly active antiretroviral therapy (HAART) will develop an exacerbation of symptoms, signs or radiological manifestations of TB that are not due to relapse or recurrence of their TB. The aetiology of these immune reconstitution inflammatory syndrome (IRIS) reactions is unknown but it is presumed that they occur, at least in part, as a consequence of HAART-related reconstitution of immunity. METHODS: Patients who were diagnosed with their first episode of definitive or presumed TB between January 2001 and July 2003 were identified from the Chelsea and Westminster TB/HIV database. The patients were classified into those who developed IRIS and those who did not using a set definition of the syndrome. Demographic, clinical and laboratory data relating to both HIV and TB were compared between the two groups. RESULTS: A total of 55 cases of TB were identified, of which 45 cases were confirmed on culture or gene probe and 10 were presumed cases. Fourteen cases (25.5%) developed IRIS with a median (range) duration of 2.53 (0.53-14.97) months. The median baseline CD4 [interquartile range (IQR)] for the IRIS group was significantly lower at 80 (33-117) cells/mm3 (P = 0.05) than the non-IRIS group at 139 (77-284) cells/mm3. A significantly greater proportion of patients in the IRIS group [11/14 (78.60%), P = 0.011] had baseline CD4 < 100cells/mm3 compared with the non-IRIS group [16/41 (39.0%)]. There was no significant difference between the two groups when comparing the log10 baseline viral load (VL). Eight (57.0%) patients in the IRIS group had disseminated TB at baseline compared with seven (17.0%) in the non-IRIS group (P = 0.006). In those who had a detectable VL at baseline, the median fold change (IQR) in CD4 from baseline to 3 months was significantly higher in the IRIS group patients, 1.5 (0.6-5.6), compared with 0.7 (-0.2 to 1.0) for those in the non-IRIS group (P = 0.046). CONCLUSIONS: Patients who develop IRIS are more likely to present with disseminated TB, have a CD4 count < 100 cells/mm3 and have a prompt rise in CD4 count in the initial 3 months of HAART.
OBJECTIVE: Topical administration of latanoprost sometimes induces gradual iris darkening. The present study was undertaken to determine if latanoprost can increase transcription of the gene for tyrosinase, an important enzyme in the biosynthesis of melanin. Results from brown, hazel, and blue irides were compared. METHODS: Iris tissue was isolated from 30 pairs of postmortem human donor eyes, and 2 iris segments from each eye were incubated in tissue culture medium supplemented with 200nM latanoprost acid or vehicle for 7 days. Tyrosinase messenger RNA (mRNA) was determined using real-time polymerase chain reaction analysis (TaqMan quantitative polymerase chain reaction). Results for tyrosinase mRNA were normalized according to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA in each sample. RESULTS: Tyrosinase mRNA expression was similar in blue and hazel irides, and ranged from 0.7-fold to 12.6-fold greater than GAPDH expression. In contrast, control brown iris culture tyrosinase expression ranged from 6.4-fold to 265-fold greater than GAPDH expression. Induction of tyrosinase mRNA by latanoprost was below threshold in all the blue iris cultures (n = 8 pairs), present in 1 of 9 hazel iris cultures, and present in 5 of 13 brown iris cultures. Mean induction in the responding hazel iris cultures was 1.40-fold. Mean induction among the responding brown iris cultures was 2.97-fold. CONCLUSIONS: These observations support the view that iris darkening associated with latanoprost treatment reflects induction of tyrosinase expression. Moreover, they suggest that the probability that latanoprost will increase tyrosinase expression is directly related to the magnitude of tyrosinase expression before treatments are initiated. CLINICAL RELEVANCE: The variability of iris darkening with latanoprost may reflect natural variation in the basal transcription of tyrosinase.
The process of lens regeneration in newts involves the dedifferentiation of pigmented iris epithelial cells and their subsequent conversion into lens fibers. In vivo this cell-type conversion is restricted to the dorsal region of the iris. We have examined the patterns of hyaluronate accumulation and endogenous hyaluronidase activity in the newt iris during the course of lens regeneration in vivo. Accumulation of newly synthesized hyaluronate was estimated from the uptake of [3H]glucosamine into cetylpyridinium chloride-precipitable material that was sensitive to Streptomyces hyaluronidase. Endogenous hyaluronidase activity was determined from the quantity of reducing N-acetylhexosamine released upon incubation of iris tissue extract with exogenous hyaluronate substrate. We found that incorporation of label into hyaluronate was consistently higher in the regeneration-activated irises of lentectomized eyes than in control irises from sham-operated eyes. Hyaluronate labeling was higher in the dorsal (lens-forming) region of the iris than in ventral (non-lens-forming) iris tissue during the regeneration process. Label accumulation into hyaluronate was maximum between 10 and 15 days after lentectomy, the period of most pronounced dedifferentiation in the dorsal iris epithelium. Both normal and regenerating irises demonstrated a high level of endogenous hyaluronidase activity with a pH optimum of 3.5-4.0. Hyaluronidase activity was 1.7 to 2 times higher in dorsal iris tissue than in ventral irises both prior to lentectomy and throughout the regeneration process. We suggest that enhanced hyaluronate accumulation may facilitate the dedifferentiation of iris epithelial cells in the dorsal iris and prevent precocious withdrawal from the cell cycle. The high level of hyaluronidase activity in the dorsal iris may promote the turnover and remodeling of extracellular matrix components required for cell-type conversion.