Aqueous Humor Drainage Research Articles

Ocular hypotensive action of topical flunarizine in the rabbit: role of sigma 1 recognition sites.

In a previous study we ascertained the presence of sigma1 and sigma2 recognition sites in the rabbit iris-ciliary body, an ocular structure involved in aqueous humor production and drainage. We characterized the sigma1 sites using the preferential ligand (+)-pentazocine, which caused a significant reduction of intraocular pressure (IOP). In the present study, flunarizine, a calcium channel blocker with a complex pharmacological profile, bound to sigma1 sites expressed in the iris-ciliary body with moderate affinity (K(i) = 68 nM). Unilateral topical flunarizine (0.01-0.1%) caused a dose-related reduction of IOP in ocular normotensive rabbits and in the alpha-chymotrypsin model of ocular hypertension, without altering the IOP of the contralateral eye. This activity was blocked by the sigma1 site antagonist NE-100 [N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine HCl] which, by itself, had no effect on IOP. Detection of flunarizine in rabbit iris-ciliary body homogenates, after topical instillation, showed that it adequately penetrates the rabbit eye. To investigate mechanisms that may contribute to ocular hypotension induced by sigma1 agonists, we carried out in vitro studies on the isolated rabbit iris-ciliary body. Flunarizine (IC50 = 5. 96 nM) and (+)-pentazocine (IC50 = 3. 81 nM) inhibited [3H]norepinephrine release. Moreover, flunarizine (IC50 = 6.34 nM) and (+)-pentazocine (IC50 = 27.26 nM) also antagonized isoproterenol-induced cAMP accumulation. The action of flunarizine and (+)-pentazocine was sensitive to NE-100 antagonism; however, this latter compound partially prevented their effect on [3H]norepinephrine and cAMP accumulation. These findings indicate that flunarizine and (+)-pentazocine interact with ocular sigma1 sites and may prove effective in the control of ocular hypertension.

Ultrasound biomicroscopy images: long-term results after deep sclerectomy with collagen implant.

The aim of this study was to understand the long-term outflow pathway mechanisms after deep sclerectomy - when collagen implant is resorbed - using ultrasound biomicroscopy (UBM). Forty-three eyes of 32 patients with medically uncontrolled open-angle glaucoma at least 1 year after deep sclerectomy were studied in an observational, non-randomised, consecutive case series. Postoperatively 15 eyes (35.7%) had goniopuncture with the Nd:YAG laser. Four eyes (9.5%) had postoperative subconjunctival injections of mitomycin C and two eyes (4.7%) had an injection of 5-fluorouracil, because of intraocular pressure (IOP) increase. Complete examination and UBM of the filtering site were performed 1-6 years after surgery. The following parameters were assessed: (1) Presence of a subconjunctival filtering bleb; (2) presence and volume of an intrascleral cavity; (3) presence of a suprachoroidal hypoechoic area. Intraocular pressure decreased significantly from 28.1+/-2.5 mmHg preoperatively to 12.4+/-3.8 (range 7-25) mmHg at the time of UBM (at least 1 year after surgery). Forty eyes showed clinically a diffuse filtering bleb. UBM demonstrated a subconjunctival space in all eyes. In 39 eyes (92.8%) an intrascleral cavity was observed. The mean volume of this cavity was 1.8 (range 0.11-6.53) mm(3). In 19 eyes (45.2%) we observed a hypoechoic area in the suprachoroidal space. UBM examination demonstrated several aqueous humour drainage pathways. A low-reflective diffuse subconjunctival space meant persistent filtration in all eyes. More than 1 year after surgery 92.8% of eyes had a remaining intrascleral cavity. In almost half of the patients an additional suprachoroidal outflow was observed, significantly correlated with a lower IOP.

Antigen retrieval of basement membrane proteins from archival eye tissues.

Antigen retrieval (AR) methods can unmask tissue antigens that have been altered by fixation, processing, storage, or resin interactions. This is particularly important in the study of archival tissues, because primary fixatives and storage times may vary among specimens. We performed an electron microscopic study of basement membrane components of the aqueous humor drainage pathways from archival eye tissue. AR (heated citrate buffer, pH 6.0, LR White resin) increased the amount of label of collagen IV and fibronectin in tissue fixed in four different fixatives, including those containing glutaraldehyde. Labeling density was approximately doubled after AR for most fixatives, with the largest increase for tissues fixed in 4% paraformaldehyde/2% glutaraldehyde. Duration of storage time for archival tissues did not affect AR results. AR did not change the components of the extracellular matrix labeled; no "new" components were labeled after AR. We conclude that AR in citrate buffer can be used on selected extracellular matrix antigens to enhance label that would otherwise be lost due to fixation and storage.

Deep sclerectomy with a collagen implant using the excimer laser

We describe a new technique of nonpenetrating glaucoma surgery that uses the excimer laser to reduce the risk of perforating the trabeculo–Descemet’s membrane. With this technique, the ablation is precise and homogeneous. A collagen device is sutured over the scleral bed to create an outflow pathway for aqueous humor drainage. After a superficial scleral flap is dissected with a diamond knife, the sclera, under direct visualization, is ablated with the excimer laser over Schlemm’s canal until aqueous humor percolates through from the anterior chamber. A collagen device is placed over the sclera to allow the aqueous humor to flow from the anterior chamber through the trabeculo–Descemet’s membrane. The preliminary results show a drop in intraocular pressure to the middle teens.

Non-secretion of mutant proteins of the glaucoma gene myocilin in cultured trabecular meshwork cells and in aqueous humor.

Until recently, very little was known about the molecular mechanisms responsible for the development of glaucoma, a leading cause of blindness worldwide. Mutations in the glaucoma gene myocilin (MYOC, GLC1A) are associated with elevated intraocular pressure and the development of autosomal dominant juvenile glaucoma and a subset of adult-onset glaucoma. MYOC is expressed in the trabecular meshwork (TM), a tissue responsible for drainage of aqueous humor from the eye, and the tissue involved in elevated intraocular pressure associated with glaucoma. To better understand the role of MYOC in glaucoma pathogenesis, we examined the expression of normal and mutant myocilin in cultured ocular (TM) and non-ocular cells as well as in the aqueous humor of patients with and without MYOC glaucoma. Normal myocilin was secreted from cultured cells, but very little to no myocilin was secreted from cells expressing five different mutant forms of MYOC. In addition, no mutant myocilin was detected in the aqueous humor of patients harboring a nonsense MYOC mutation (Q368X). Co-transfection of cultured cells with normal and mutant myocilin led to suppression of normal myocilin secretion. These studies suggest that MYOC glaucoma is due either to insufficient levels of secreted myocilin or to compromised TM cell function caused by congestion of the TM secretory pathway.

Treating Glaucoma with Drainage Devices and Pericardial Grafts

Glaucoma is caused by a sustained elevation of intraocular pressure due to the decreased drainage of aqueous humor from the anterior chamber of the eye. There are many types of glaucoma, which, if left untreated, may have devastating results for the patient. Glaucoma can remain uncontrolled after medical and surgical interventions. Glaucoma drainage device implants with pericardial graft placements often are helpful in relieving the effects of glaucoma and increasing the patient's quality of life.

NEW PERSPECTIVES IN SELECTIVE TRABECULAR SURGERY

Enormous progress has been made in understanding the complexity of the underlying causes of chronic open-angle glaucoma; however, indisputable concepts for effective treatment are still rare. To date, conventional filtering surgery remains the mainstay of surgical therapy in the management of glaucoma not controlled by medication. 25 Unfortunately, treatments involving full-thickness filtration are scarcely selective, as healthy structures not primarily involved in the disease process are subject to surgical intervention. The application of adjunct antimetabolites for inhibition of undesired episcleral fibroblastic proliferation dramatically increased the success rates for filtering procedures but had the disadvantage of exacerbating serious side effects, such as flat anterior chambers, prolonged postoperative hypotony, and late endophthalmitis from infected filtering blebs. 27,45 Microsurgery on Schlemm's canal and the human aqueous outflow system for controlling intraocular pressure (IOP) in chronic open-angle glaucoma have been evolving over the past few decades. Theoretic considerations indicate that production of approximately 10 to 15 fistulae, each 10 μm in diameter, between the anterior chamber and Schlemm's canal should restore normal outflow facility in open-angle glaucoma. 9 The basis for most of the current approaches to microsurgery of Schlemm's canal is the finding by Grant 10 that the largest proportion of resistance to outflow is located within the trabecular meshwork, namely, the cribriform layer and can be eliminated by incising the trabecular meshwork and entering the canal of Schlemm. If one agrees that the site of the pathologic resistance to aqueous humor outflow is this tissue, then partial removal, taking the utmost possible care not to damage the surrounding chamber angle structures, could be a new alternative in antiglaucomatous surgery. This sort of selective nonpenetrating trabecular surgery would be equivalent to internal filtration surgery without transscleral drainage of aqueous humor into the subconjuntival space and would thereby reduce the incidence of postoperative complications typically associated with filtering procedures. This review discusses different internal trabecular microsurgical techniques that are designed to facilitate outflow along its natural pathway. Each new technique is described in detail, newly developed instrumentation is discussed, and the presumed mechanisms of action are outlined. The reader must understand, however, that none of these new microsurgical procedures threaten to replace conventional filtering approaches, as they are still in the experimental phase and under careful clinical evaluation, and there is plenty of room left for further refinements and developments. We hope this article gives us impetus to the search for alternative strategies in antiglaucomatous surgery and focuses attention more closely on the diseased target structure in chronic open-angle glaucoma: the trabecular meshwork.

血液透析と眼圧

Hemodialysis, a useful treatment for patients with severely compromised renal function, has also unfavorable side effects. In the ophthalmologic area, a rise in intraocular pressure (IOP) during dialysis accompanied by ocular pain has been reported. In our study when measuring IOP, as well as serum osmolality and plasma CO2 pressure every 30 minutes during routine hemodialysis in renal failure patients with a normal aqueous outflow facility, the mean percent changes of IOP to the initial value showed no significant difference at any time, although the changes in serum osmolality decreased significantly. The mean percent changes of plasma CO2 pressure also did not show any significant difference during dialysis. In patients with a poor aqueous outflow facility, the mean percent changes of IOP increased significantly after 90 minutes, with the exception of the change at 180 minutes. The mean percent changes of serum osmolality decreased significantly after starting dialysis. A negative correlation in the mean percent change of IOP with that of serum osmolality was detected. The administration of an intravenous hyperosmotic agent prevented significant changes not only in serum osmolality but also in IOP. Therefore, it is considered that hemodialysis causes a decrease in serum osmolality, resulting in an osmotic gradient between the plasma and the intraocular fluids due to the presence of the blood-ocular barrier. Although the osmotic gradient draws water from the plasma into the eye, if there is no abnormal obstruction in the aqueous outflow pathway, an amount of aqueous humor matching the increase in intraocular fluid goes through the pathway out of the eye to maintain the normal level of IOP. In eyes with an obstructed aqueous outflow pathway, however, this compensatory mechanism of aqueous humor drainage does not work well, and results in an IOP elevation.

Effects of ethacrynic acid on intraocular pressure of anesthetized rats.

Ethacrynic acid (ECA) lowers intraocular pressure (i.o.p.) by an effect usually ascribed to increased drainage of aqueous humor by the trabecular meshwork. Here, we describe the effects of a continuous 2-hr intracameral infusion of balanced salt solution (BSS), with or without 2 mM ECA (sodium salt), on IOP of pentobarbital anesthetized rats. The infusion was divided into a constant (0.05 microliter/min) and a periodic (0.25 microliter/min) component that cycled 4 min on then 4 min off. This permitted the calculation of dynamic changes in resistive (trabecular and uveoslceral drainage) and nonresistive (aqueous synthesis, episcleral venous pressure) components of IOP by fitting a second-order transfer function to the responses. ECA markedly blunted the BSS-induced rise in IOP (P < 0.01). The rise in resistive mechanisms (ocular impedance) was transiently blunted by ECA (P < 0.05) during the third and fourth 8-min cycles, and nonresistive mechanisms were reduced by ECA from cycles 3-10 (P < 0.05). Then, at the end of the infusion, the control and ECA dynamic values were similar (P < 0.05), although IOP of ECA-treated rats was still slightly reduced (P < 0.05). The most likely explanation is a summation of small changes in both resistive and nonresistive components of IOP dynamics. Systemic blood pressure was unchanged within either group. The well-known effects of ECA on the trabecular meshwork, alone, are insufficient to explain the dynamic changes in IOP observed in this model.

Effects of Ethacrynic Acid on Intraocular Pressure of Anesthetized Rats

Ethacrynic acid (ECA) lowers intraocular pressure (IOP) by an effect usually ascribed to increased drainage of aqueous humor by the trabecular meshwork. Here, we describe the effects of a continuous 2-hr intracameral infusion of balanced salt solution (BSS), with or without 2 mM ECA (sodium salt), on IOP of pentobarbital anesthetized rats. The infusion was divided into a constant (0.05 μl/min) and a periodic (0.25 μl/min) component that cycled 4 min on then 4 min off. This permitted the calculation of dynamic changes in resistive (trabecular and uveoslceral drainage) and nonresistive (aqueous synthesis, episcleral venous pressure) components of IOP by fitting a second-order transfer function to the responses. ECA markedly blunted the BSS-induced rise in IOP (P < 0.01). The rise in resistive mechanisms (ocular impedance) was transiently blunted by ECA (P < 0.05) during the third and fourth 8-min cycles, and nonresistive mechanisms were reduced by ECA from cycles 3-10 (P < 0.05). Then, at the end of the infusion, the control and ECA dynamic values were similar (P > 0.05), although IOP of ECA-treated rats was still slightly reduced (P < 0.05). The most likely explanation is a summation of small changes in both resistive and nonresistive components of IOP dynamics. Systemic blood pressure was unchanged within either group. The well-known effects of ECA on the trabecular meshwork, alone, are insufficient to explain the dynamic changes in IOP observed in this model.

Aqueous humor dynamics in beagle dogs with caffeine-induced ocular hypertension.

In order to investigate the possible mechanisms for caffeine-induced ocular hypertension, the intraocular pressure (IOP) and the outflow through the trabecular meshwork were measured in beagle dog eyes after dosing with intravenous caffeine (30 mg/kg) alone or in combination with the topical beta-blocker befunolol [applied as 100 microliters of a 1% (w/v) solution] which inhibits aqueous humor formation in the ciliary body. Intravenous injections of caffeine significantly increased the IOP at 0.25 and 1 hr after a single dose. The ocular hypertension recovered within 2 hr following dosing. Over time, there were no differences in the outflow between the caffeine and control groups. The instillation of befunolol lowered outflow and produced ocular hypotension. The levels of the IOP and outflow in dogs treated with caffeine and befunolol in combination were almost the same as those in dogs treated with befunolol alone. Single-dose and combination-dose studies demonstrate that intravenous caffeine increases the IOP in normal beagle dogs possibly by increasing aqueous humor formation and not by the inhibition of aqueous humor drainage through the trabecular meshwork.

Ultrasound biomicroscopy of eyes undergoing deep sclerectomy with collagen implant.

To assess the intraocular pressure (IOP) lowering mechanism of deep sclerectomy with collagen implant (DSCI), a non-penetrating glaucoma surgery. Nine eyes of nine patients with medically uncontrolled open angle glaucoma underwent DSCI. Ultrasound biomicroscopy (UBM) of the sclerectomy site was performed 1 month after surgery. The following factors were assessed: length and height of collagen implant, and thickness of the residual trabeculocorneal membrane. Postoperative IOP decreased significantly in all nine eyes from a preoperative mean value of 25.8 (SD 4.8) mm Hg to a postoperative (1 month) mean value of 11.3 (6.3) mm Hg (p = 0.001). In all nine eyes, UBM at 1 month after surgery showed a subconjunctival filtration through the thin trabeculocorneal membrane and through the scleral flap around the collagen implant. In four cases, a hypoechoic area in the suprachoroidal space was observed and might represent ciliary body detachment or be due to suprachoroidal drainage of aqueous humour through the thin deep scleral wall. At 1 month after surgery the mean trabeculocorneal membrane thickness was 110.1 (16.8) microns, and the mean length and height of the collagen implant were 2.3 (0.1) mm and 1.1 (0.1) mm respectively. DSCI lowered IOP by allowing aqueous filtration through a thin trabeculocorneal membrane to the subconjunctival space and, eventually, to the suprachoroidal space.

Training in relaxation and visual imagery with patients who have open-angle glaucoma

This study investigated the effects of training in relaxation and visual imagery on the intraocular pressure (IOP) of patients suffering from primary open angle glaucoma. The treatment included a basic program (BP) of standard autogenic relaxation exercises and an advanced program (AP), in which patients received instructions and practice regarding special exercises in ocular relaxation and imagination of aqueous humor drainage. Twenty-three patients, aged 24 to 69 years, received assignment either to a training group or to a waiting-list control group. We measured IOP before and after each training session. We ascertained 24-hr IOP profiles during clinical assessments prior to the training, in the interval between the BP and the AP, and after termination of the training. We also performed the water drinking test to provoke maximum IOP levels, and patients completed psychological questionnaires of depression, anxiety, and physical complaints. Results on short-term changes indicate only slight improvements of IOP levels following each training session. However, during the course of the BP as well as of the AP, we detected a significant decrease in IOP. Twenty-four-hour profiles as well as the water drinking test also showed significant reductions of IOP across time. Medication dosage decreased for 56% of the initially treated patients. The findings suggest that relaxation and visual imagery techniques can be beneficial in reducing elevated IOP levels in patients with open angle glaucoma.

The development of Schlemm's canal from aspects of the aqueous humor drainage

We have investigated the development of Schlemm's canal using human eyes. We have also examined whether the endothelium of Schlemm's canal hasWeibel-Palade bodies and blood coagulation factor VIII-related antigen in human and monkey eyes. The deep scleral vessels first grew towards the trabecular meshwork and then changed direction to grow circumferentially. This fact suggests that there may be interactions between the scleral vessels and the trabecular meshwork for the circumferential growth of Schlemm's canal. BothWeibel-Palade bodies and factor-VIII antigen were detected in the endothelium of Schlemm's canal. These results indicate that Schlemm's canal is derived from blood vessels. It is also suggested that the damaged endothelium of Schlemm's canal may be repaired in the same way as the endothelium of blood vessels.

Beta-human chorionic gonadotropin, progesterone, and aqueous dynamics during pregnancy.

To determine whether the altered hormonal milieu of pregnancy is associated with changes in the dynamics of aqueous humor formation and drainage. Nineteen women were studied during each trimester of a single pregnancy and post partum. Measures of aqueous dynamics included intraocular pressure, aqueous flow, facility of outflow, aqueous flare, and corneal thickness. Pregnancy was associated with relatively lower intraocular pressure, reduced aqueous flare, increased corneal thickness, and increased aqueous outflow facility. Aqueous flow was unchanged. The progesterone level increased during pregnancy and decreased during the postpartum period. The beta-human chorionic gonadotropin level was highest during the first trimester. The progesterone level, but not the beta-human chorionic gonadotropin level, was correlated with intraocular pressure, aqueous flare, and corneal thickness. The change in aqueous outflow facility that accompanied pregnancy could not be correlated directly to changes in beta-human chorionic gonadotropin or progesterone concentrations. Aqueous flow remains constant during and after pregnancy, but intraocular pressure decreases during pregnancy due to an increase in the outflow facility. The changes in aqueous dynamics are consistent with the hypothesis that excess progesterone during pregnancy blocks the ocular hypertensive effect of endogenous corticosteroids. However, we were unable to find a statistically significant correlation when a direct comparison between the observed changes in outflow facility and the observed changes in the progesterone level was made, perhaps because of intersubject variability of these changes. The changes in intraocular pressure and outflow facility could have been due to one of many other changes in pregnancy that were not measured.

In Vivo Observations of the Episcleral Vasculature in the Albino Rabbit

The recently described arteriovenous anastomoses of the episcleral vasculature were studied in the albino rabbit by in vivo microscopy and microendoscopy. The arteriovenous anastomoses lead directly into the episcleral venous plexus which drains aqueous humor via well-visible aqueous veins. In the arteriolar segment of the arteriovenous anastomoses the blood flow velocity, measured by intra-arterial bolus injections of Evans blue, decreases drastically toward the venular segment of the arteriovenous anastomoses. After topical application of epinephrine, the arteriolar segment contracts faster and to a greater degree than all other parts of the episcleral vasculature. In the aqueous veins this stoppage of the blood inflow from the arteriovenous anastomoses may allow an increase in the amount of aqueous humor drained from the anterior chamber. The simultaneously measured intraocular pressure decreases significantly. Experimental elevation of the intraocular pressure from 18 to 30 mm Hg causes a decrease in diameter and blood flow in the arteriovenous anastomoses. These effects are reversed by returning to normal intraocular pressure levels. It is assumed that the arteriovenous anastomoses play a role in aqueous humor drainage by the episcleral venous plexus.

Functional Morphology of the Episcleral Vasculature in Rabbits and Dogs

Scanning electron microscopic analysis of corrosion casts of the intra- and episcleral vasculature in the limbic region of two species (rabbit and dog) revealed typical arteriovenous anastomoses representing shunts between the long radial arterioles, branches of the anterior ciliary arteries, and the episcleral venous plexus. The arteriovenous anastomoses consist of a small arteriolar segment and a wide, funnel-like venous segment. Using immunohistochemical techniques it was shown that the wall of the arteriolar segment consists of smooth muscle cells containing alpha-smooth muscle actin. In the dog, the vessel wall of the arteriovenous anastomoses also contain typical epithelioid cells, the structure of which was analyzed by transmission electron microscopy. In the episcleral vasculature, a capillary network is lacking, an elaborate wide venous plexus is developed instead. It is assumed that this plexus with the help of the newly described arteriovenous anastomoses may influence aqueous humor drainage and thereby also intraocular pressure.

Bilateral intraoculár pressure elevation and decrease of facility of aqueous humour outflow as a consequence of regional lymphoedema of head and neck

Aqueous humour drainage to the deep cervical lymphatics has been proven in animal experiments, but there have been no observations of changes in intraocular pressure (IOP) or aqueous humour drainage as a consequence of lymph drainage dysfunction. The history of a patient with non-Hodgkin's lymphoma, who underwent a left-sided radical neck dissection in January 1991, is reported. From the end of 1991 lymphoedema of the head and neck, predominantly on the right side, developed without venous stasis but with significant bilateral IOP elevation and aqueous humour outflow reduction, refract to conventional treatment. Two days after cytostatic treatment the lymphoedema disappeared, and IOP and aqueous humour outflow became normal. Four days later the patient died because of an acute bronchopneumonia. The pathological examination revealed an intact internal jugular venous system, enlarged lymph nodes and, as a consequence of previous irradiation, cicatrization in the right side of the neck. On the left side, there was absence of the internal jugular vein and jugular lymphatic trunk due to previous radical neck dissection. Our case suggests that regional lymphatic stasis and the absence of the collateral drainage to the contralateral side significantly reduces the aqueous humour outflow and leads to a bilateral, secondary IOP elevation.

Some aspects of aqueous humour drainage

It is now 50 years since the discovery of the aqueous veins by Karl Ascher. His finding had a great impact on ophthalmology since it showed that the aqueous humour is not a stagnant fluid; there had to be a continuous formation of aqueous humour by the ciliary processes, flow from the posterior chamber into the anterior chamber and outflow in the chamber angle. Since that time it has become clear that there is also some drainage of aqueous humour via uveoscleral routes. Furthermore the flow through the inner wall of Schlemm's canal has been shown to take place through about 20,000 pores each with diameter of around 0.1-3 microns. Recent measurements of the pressures in the outflow routes indicate that in normal monkey eyes the main outflow resistance is located close to the inner wall of the canal. Most of the aqueous humour leaving Schlemm's canal via the collector channels mixes with blood within the sclera. This is a consequence of the embryology of Schlemm's canal; it develops by the merging of blind extensions from intrascleral veins. Despite its specialisation the endothelium of Schlemm's canal retains the properties of a blood vessel. Platelets are likely to play in role in the integrity of Schlemm's canal as they do in blood vessels and may in fact control the size of the pores by occluding pores larger than 3 microns. It seems likely that in vitro perfusion of glaucomatous eyes with enzymes may be useful in the search for new methods of treatment for glaucoma.

Age changes in rhesus monkey ciliary muscle: Light and electron microscopy

The ciliary muscle from 44 rhesus monkeys ranging in age from 137-day fetuses and a 3-week neonate to 35-year-old adults was studied by light and electron microscopy. In the fetuses and the neonate, the muscle cells appeared immature, and the muscle consisted mainly of longitudinally oriented fibers. By age 1 year, the muscle fibers were aggregated into bundles, and within each bundle the individual fibers were packed tightly together. In saggital section, the muscle now exhibited longitudinal, reticular and circular portions. The individual muscle cells exhibited ultrastructural characteristics which set them apart from other smooth muscle cells. Age-related structural changes occurred in the ciliary muscle and intramuscular nerves, beginning at 6 years. These included increasing numbers of lysosomes, ‘fingerprints’, and the appearance of myelin figures within some nerve endings and nerve fibers. These alterations became more frequent and pronounced with age, and in elderly animals were seen in all regions of the muscle and around its entire circumference. Additionally, the elderly animals exhibited overt degeneration of some muscle cells and some myelinated nerve fibers. The time-course of these age-related structural neuromuscular alterations parallels the decline of functional accommodative amplitude (i.e. presbyopia) and of the ciliary muscle's configurational response to peripheral pharmacologic and central electrical stimulation. This suggests a pathophysiologic, albeit (given the relatively moderate overall abnormalities) not necessarily causal, relationship. An age-related increase in the number of pigmented cells between the ciliary muscle bundles also occurred, with the anterior longitudinal region being affected last. This might reflect an age-related decline in uveoscleral drainage of aqueous humor.