Aqueous Humor Pressure Research Articles

Implementing new computational methods for the study of JCT and SC inner wall basement membrane biomechanics and hydrodynamics

PurposeThe conventional aqueous outflow pathway, which includes the trabecular meshwork (TM), juxtacanalicular tissue (JCT), and the inner wall endothelium of Schlemm's canal (SC), regulates intraocular pressure (IOP) by controlling the aqueous humor outflow resistance. Despite its importance, our understanding of the biomechanics and hydrodynamics within this region remains limited. Fluid-structure interaction (FSI) offers a way to estimate the biomechanical properties of the JCT and SC under various loading and boundary conditions, providing valuable insights that are beyond the reach of current imaging techniques. MethodsIn this study, a normal human eye was fixed at a pressure of 7 mm Hg, and two radial wedges of the TM tissues, which included the SC inner wall basement membrane and JCT, were dissected, processed, and imaged using 3D serial block-face scanning electron microscopy (SBF-SEM). Four different sets of images were used to create 3D finite element (FE) models of the JCT and inner wall endothelial cells of SC with their basement membrane. The outer JCT portion was carefully removed as the outflow resistance is not in that region, leaving only the SCE inner wall and a few µm of the tissue, which does contain the resistance. An inverse iterative FE algorithm was then utilized to calculate the unloaded geometry of the JCT/SC complex at an aqueous humor pressure of 0 mm Hg. Then in the model, the intertrabecular spaces, pores, and giant vacuole contents were replaced by aqueous humor, and FSI was employed to pressurize the JCT/SC complex from 0 to 15 mm Hg. ResultsIn the JCT/SC complex, the shear stress of the aqueous humor is not evenly distributed. Areas proximal to the inner wall of SC experience larger stresses, reaching up to 10 Pa, while those closer to the JCT undergo lower stresses, approximately 4 Pa. Within this complex, giant vacuoles with or without I-pore behave differently. Those without I-pores experience a more significant strain, around 14%, compared to those with I-pores, where the strain is roughly 9%. ConclusionsThe distribution of aqueous humor wall shear stress is not uniform within the JCT/SC complex, which may contribute to our understanding of the underlying selective mechanisms in the pathway.

Measurement of vitreous humor pressure in vivo using an optic fiber pressure sensor

We conducted a study to assess the pressure difference between the aqueous and vitreous humors in rabbit eyes using a direct intraocular pressure (IOP) measurement method. A micro-optic-fiber pressure sensor was utilized for this purpose. Preliminary experiments with enucleated porcine eyes confirmed the sensor's accuracy in measuring both aqueous and vitreous humor pressure. The main study involved six healthy albino rabbits, where the sensor measured the pressure in the anterior chamber (aIOP) and posterior vitreous-cavity (pIOP). These measurements were compared to aIOP values obtained through rebound tonometry. Additionally, pre- and postoperative pressure comparisons were made after performing a vitrectomy. Results revealed a significant disparity between aqueous and vitreous humor pressures. Prior to vitrectomy, pIOP was 22.8 mmHg, over twice as high as aIOP (11.0 mmHg), but decreased to a similar level following the procedure. Comparison between the sensor measurements and rebound tonometry showed agreement in aIOP values. In conclusion, our study demonstrates that vitreous humor pressure is consistently higher than aqueous humor pressure, reaching the upper limit of normal IOP. Furthermore, vitrectomy effectively reduces pIOP, aligning it with aIOP. These findings contribute valuable insights into intraocular pressure dynamics and have implications for clinical interventions targeting ocular pressure regulation.

Viscoelastic Biomechanical Properties of the Conventional Aqueous Outflow Pathway Tissues in Healthy and Glaucoma Human Eyes.

Background: Although the tissues comprising the ocular conventional outflow pathway have shown strong viscoelastic mechanical response to aqueous humor pressure dynamics, the viscoelastic mechanical properties of the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and Schlemm’s canal (SC) inner wall are largely unknown. Methods: A quadrant of the anterior segment from two human donor eyes at low- and high-flow (LF and HF) outflow regions was pressurized and imaged using optical coherence tomography (OCT). A finite element (FE) model of the TM, the adjacent JCT, and the SC inner wall was constructed and viscoelastic beam elements were distributed in the extracellular matrix (ECM) of the TM and JCT to represent anisotropic collagen. An inverse FE-optimization algorithm was used to calculate the viscoelastic properties of the ECM/beam elements such that the TM/JCT/SC model and OCT imaging data best matched over time. Results: The ECM of the glaucoma tissues showed significantly larger time-dependent shear moduli compared to the heathy tissues. Significantly larger shear moduli were also observed in the LF regions of both the healthy and glaucoma eyes compared to the HF regions. Conclusions: The outflow tissues in both glaucoma eyes and HF regions are stiffer and less able to respond to dynamic IOP.

The role of low intracranial pressure in the development of glaucoma in patients with Alzheimer's disease

October 22, 2013Dear Editor,We read with great interest the paper by Janssen et al. (2013)entitled ‘The vast complexityof primaryopen angle glaucoma: Dis-ease genes, risks, molecular mechanisms and pathobiology.’ Theauthors deserve appreciation for their very informative reviewarticle.However,wewishtomakeacommentconcerningtheirdis-cussion of the potential role of intracranial pressure (ICP) in Alz-heimer’s disease (AD) and glaucoma.In the last section of their paper, Janssen and colleaguesdiscuss the potential relation between primary open angle glau-coma (POAG) and AD. As the authors mention, several studieshave found an increase in the occurrence of glaucoma in AD pa-tients. The authors state: “In our view, POAG damage could becaused by the net pressure over the optic disk, involving boththe aqueous humor pressure of the eye and cerebrospinal fluid(CSF) pressure of the brain, as described above. Also, CSF pressurechanges have been described in AD (Silverberg et al., 2006).Could these pressure changes underlie a relationship betweenPOAG and AD, and at the same time explain the apparently con-flicting association studies?” Further, the authors state: “We hy-pothesize that there is a strong association between normalpressure glaucoma and late AD, since both disease stages,following the ‘net pressure on the optic disk hypothesis’,arecharacterized by one single disease mechanism: an abnormallylow ICP.”Janssen et al. (2013) thus hypothesize that low ICP may play arole in the association between glaucoma and AD. We fully agreewith the authors since our group has previously presented this hy-pothesisforthefirsttime(Wostynetal.,2008,2009a).Intwoofourearlier manuscripts published in 2008 (Wostyn et al., 2008) and2009 (Wostyn et al., 2009a), we proposed low ICP occurring inAD as a factor leading to increased risk of glaucoma. Evidence forthishypothesiswasgainedfromCSFpressuremeasurementstudiesin AD patients and patients with glaucoma. The finding of a highoccurrence of reduced CSF pressure among patients with AD(Silverberg et al., 2006; Wostyn et al., 2009b) could be linked tothe high rate of reported comorbidity between AD and glaucoma(Bayer et al., 2002; Tamura et al., 2006), since it has been shownthat CSF pressure is lower in patients with glaucoma (Berdahlet al., 2008a, 2008b; Ren et al., 2010). This could result in anabnormally high trans-lamina cribrosa pressure difference andlead to glaucomatous damage. Given this previously advanced hy-pothesis, it was a great surprise when Janssen et al. (2013) recentlyhypothesized about the potential role of low ICP in glaucoma andAD without citing our earlier work (Wostyn et al., 2008, 2009a)or making clear the relevant precedents. The authors did cite oneof our papers, one largely focused on the high occurrence rate ofglaucoma among patients with normal pressure hydrocephalus(Wostyn et al., 2010), but this paper has no direct relevance tothe above hypothesis.Sincerely yours,Peter Wostyn, MDVeva De Groot, MD, PhDDebby Van Dam, PhDKurt Audenaert, MD, PhDPeter Paul De Deyn, MD, PhDReferences

Naphazoline-induced Suppression of Aqueous Humor Pressure and Flow: Involvement of Central and Peripheral α2/I1Receptors

The objective of this study was to examine the ocular hydrodynamic effects of topically and centrally administered naphazoline, alone and following pretreatment with pertussis toxin (PTX) and α2/I1receptor antagonists. Topically and intracisternally administered naphazoline was examined for its ability to alter intraocular pressure (IOP) of rabbits in the absence and presence of receptor antagonists (rauwolscine, efaroxan) and a Gi/oribosylating agent PTX. In addition, the topical effects of naphazoline on pupil diameter and aqueous humor flow rate were evaluated. Topical unilateral application of naphazoline (7.5, 25 and 75μ g; 25μ l) elicited an ipsilateral dose-dependent mydriasis (2, 4 and 5.5mm) that peaked at 2hr with a duration of up to 5hr. The IOP decreases induced by naphazoline were bilateral and dose-dependent (3, 6 and 10mmHg); the response peaked at 1hr and lasted for up to 5hr. Pretreatment with efaroxan (250μ g) elicited significantly greater antagonism of the ocular hypotensive response to naphazoline than did rauwolscine (250μ g) suggesting an involvement of imidazoline (I1) receptors. Intracisternal application of naphazoline (3.3μ g) also produced bilateral reductions (6mmHg) of IOP that were immediate (10min post drug) and lasted for approximately 2hr. In PTX-pretreated (2.5μ gkg−1, i.a.) rabbits, the ocular hypotensive effects of naphazoline by both routes (topically and centrally) were attenuated by 50–65%. In addition to producing ocular hypotension, topical application of naphazoline (75μ g; 25μ l) caused significant reduction, from 2.8 to 1.5μ lmin−1, in aqueous humor flow. These in vivo data indicate that, regardless of route of administration, alteration of aqueous humor flow by naphazoline was induced by the activation of α2and I1receptors. The ocular hypotensive effects produced by central administration did not result in sedation, therefore, there is the suggestion that central α2adrenergic receptors were stimulated minimally by naphazoline. Thus, these data suggest that ocular hypotensive effects and suppression of aqueous humor flow rate by naphazoline are mediated, in part, by α2and/or central I1at both central (brain) and peripheral (eye) sites. Moreover, these data indicate that the receptors are linked to PTX-sensitive G(i/o)proteins.

Intraocular pressure in anaesthetized dogs given flumazenil with and without prior administration of midazolam

This study examined the effect of flumazenil, a benzodiazepine antagonist, on aqueous humour pressure in dogs receiving either midazolam or no benzodiazepine. Twenty-four halothane-anaesthetized dogs were assigned to one of four groups. Group I (n = 6) received saline iv at 0, 45 and 90 min. Group 2 (n = 6) received saline at 0 min, flumazenil 0.0025 mg.kg-1 iv at 45 min and flumazenil 0.16 mg.kg-1 at 90 min. Group 3 (n = 6) received midazolam 1.6 mg.kg-1 at 0 min followed by continuous iv infusion (1.25 mg.kg-1.hr-1). Flumazenil was given at 45 and 90 min as in Group 2. In Group 4 (n = 6) aqueous humour pressure was elevated to about 35 mmHg then midazolam and flumazenil were given as in Group 3. Aqueous humour pressure was determined using a 30-gauge needle placed into the anterior chamber. Saline or flumazenil produced no change in aqueous humour pressure in Groups 1 and 2. In Groups 3 and 4, midazolam decreased aqueous humour pressure from 18 +/- 2 mmHg (mean +/- SD) to 14 +/- 3 mmHg (P less than 0.001) and from 34 +/- 5 mmHg to 31 +/- 3 mmHg (P less than 0.01) respectively. Flumazenil given during continuous infusion of midazolam produced increases of aqueous humour pressure of 2 +/- 1 (P less than 0.01) to 5 +/- 2 mmHg (P less than 0.01) that lasted less than or equal to 12 min. It is concluded that at both normal and elevated aqueous humour pressures flumazenil produces statistically significant but clinically unimportant increases of aqueous humour pressure in anaesthetized dogs receiving midazolam, but not in dogs given no benzodiazepine.