Ocular tissue

Because Raman signals are typically weak, intense lasers in combination with sophisticated tight collection must be used. Although intense laser radiation can potentially harm the delicate structures in the visual system, ocular tissue has been found to be a very suitable target for Raman spectroscopy for two reasons. First, the ocular media (cornea, lens and vitreous) generally have good optical clarity, which enables high penetration of laser excitation and optical detection of scattered 

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Anand et al. 1987). The authors hypothesized that the ocular effects associated with endosulfan may be a result of prolonged hypertension (although no data on blood pressure were presented, and there is no other information to indicate that chronically administered endosulfan induces hypertension) or an endosulfan-induced vitamin A deficiency (which was observed in this study). Although the rabbit may represent a uniquely sensitive species, the possibility that long-term exposure of persons at hazardous waste sites to endosulfan may result in adverse effects on ocular tissues cannot be eliminated. 

Atalla, L. Scvanian, A. and Rao, N. (1988). Hydrogen peroxide localization in ocular tissue an electron microscope cytochemical study. Curr. Eye Res. 7, 931-936. 

Instruct patients over the phone to irrigate the eye immediately with water or saline continuously for at least 15 minutes before seeking a clinician. Irrigation dilutes and removes the chemical agent, and is the best way to decrease ocular tissue damage. Patients should then seek immediate care from an ophthalmologist or emergency facility.7... 

Fig. 2 Specular microscope setup for in vitro evaluation of effect of drugs on ocular tissue. 

The conventional concentration of benzalkonium chloride in eyedrops is 0.01%, with a range of 0.004-0.02% [111]. While uptake of benzalkonium chloride itself into ocular tissues is limited [113], even lower concentrations of benzalkonium chloride have been reported to enhance corneal penetration of other compounds including therapeutic agents [93,112,114]. The differential effect of this preservative on the cornea compared to the conjunctiva can be exploited to target a drug for corneal absorption and delivery to the posterior segment of the eye [115]. Its use has been proposed as a means of delivering systemic doses by an ocular route of administration [116]. 

This preservative is comparatively new to ophthalmic preparations and is a polymeric quaternary ammonium germicide. Its advantage over other quaternary ammonium seems to be its inability to penetrate ocular tissues, especially the cornea. It has been used at concentrations of 0.001-0.01% in contact lens solutions as well as dry eye products. At clinically effective levels of preservative, POLYQUAD is approximately 10 times less toxic than benzalkonium chloride [87,137], Various in vitro tests and in vivo evaluations substantiate the safety of this compound [137,141,142], This preservative has been extremely useful for soft contact lens solutions because it has the least propensity to adsorb onto or absorb into these lenses, and it has a practically nonexistent potential for sensitization. Its ad-sorption/absorption with high water and high ionic lenses can be resolved by carefully balancing formulation components [143],... 

These include absorption by adjacent palpebral and bulbar conjunctiva, with concomitant rapid removal from ocular-tissues by peripheral blood flow. For example, the extensive vascularity of the uvea underlies the bulbar conjunctiva, a mucous membrane, and the sclera, a white tissue providing a tough outer covering [177]. Binding of drug to either external sites, like the tear polymers such as mucins or lysozyme, or internal tissues like the sclera can be detrimental to efficacy. 

An ophthalmic suspension should use the drug in a microfine form usually 95% or more of the particles have a diameter of 10 pm or less. This is to ensure that the particles do not cause irritation of the sensitive ocular tissues and that a uniform dosage is delivered to the eye. Since a suspension is made up of solid particles, it is at least theoretically possible that they may provide a reservoir in the cul-de-sac for slightly prolonged activity. However, it appears that this is not so, since the drug particles are extremely small, and with the rapid tear turnover rate they are washed out of the eye relatively quickly. 

The choice of a particular inactive ingredient and its concentration is based not only on physical and chemical compatibility, but also on biocompatibility with the sensitive and delicate ocular tissues. Because of the latter requirement, the use of inactive ingredients is greatly restricted in ophthalmic dosage forms. 

The carbomer polymeric gel base itself has been used successfully to treat moderate to severe cases of dry eye (keratoconjunctivitis sicca) [282]. The dry eye syndrome is usually characterized by deficiency of tear production and, therefore, requires frequent instillation of aqueous artificial tear eyedrops to keep the corneal epithelium moist. The gel base applied in a small amount provides a prolonged lubrication to the external ocular tissues, and some patients have reduced the frequency of dosing to control their symptoms to three times a day or fewer. 

Although the ocular absorption of peptide as well as nonpeptide drugs is poor [96,196-198], the ocular route is by far the least studied for the usefulness of penetration enhancers. This is in part due to the perceived sensitivity of ocular tissues to irritation and the fear of corneal and conjunctival damage caused by the enhancers. Whereas the rat nasal epithelium may tolerate up to 5% sodium glycocholate [199], ocular administration of sodium glycocholate at a concentration of 2% and beyond induces reddening of the eye and tear production in rabbits (Kompella and Lee, unpublished observation). 

DM Maurice. (1976). Techniques of investigation of the cornea. In S Dikstein, ed. Drugs and Ocular Tissues. Basel Krager, pp. 90-101. 

Khachik, F, de Moura, FF, Zhao, DY, Aebischer, CP, and Bernstein, PS, 2002. Transformations of selected carotenoids in plasma, liver, and ocular tissues of humans and in nonprimate animal models. Invest Ophthalmol Vis Sci 43, 3383-3392. 

Provost, AC, Pequignot, MO, Sainton, KM, Gadin, S, Salle, S, Marchant, D, Hales, DB, and Abitbol, M, 2003. Expression of SR-BI receptor and StAR protein in rat ocular tissues. C R Biol 326, 841-851. 

It is well known that 1,10-phenanthrolines are highly active ironchelating agents. The parent compound itself has recently been shown to increase HIF-la levels in ocular tissue and to suppress 02-mediated epithelial cell proliferation when administered to mice [29]. A quantitative assay was developed to measure transcriptional potency of certain HIF stabilizers via an HRE-mediated (3-lactamase production in which the EC50 of 1,10-phenanthroline was measured to be approximately 8 pM. In addition, VEGF was dose-dependently produced in mouse embryonic fibroblasts by 1,10-phenanthroline with an EC50 of... 

Newsome A, Stern R. Pilocarpine adsorption by serum and ocular tissues. Am J Ophthalmol 77 918-922 (1974). 

Scholz M, Lin JE, Lee VE1, Keipert S. Pilocarpine permeability across ocular tissues and cell cultures Influence of formulation parameters. J Ocul Pharmacol Ther 18 455-468 (2002). 

Figure 13.1 A cross-sectional representation of the ocular surface, highlighting the conjunctival tissue as a thick black contour. Three distinct areas of the conjunctiva are labeled along with adjacent ocular tissues.

A variety of automatic voltage clamp devices with special modifications have been extensively utilized in electrophysiological studies of /sc in several ocular tissues including the amphibian corneal epithelium [42] and human fetal retinal pigment epithelium [43, 44], as well as non-ocular tissues like the rat tracheal epithelium [45], A strong temperature dependency and inhibitory effect of serosally instilled ouabain on the rabbit conjunctival /sc are characteristic of active ion transport driven by Na+/K+-ATPases in the conjunctiva [6, 7],... 

Found in ocular tissues immunoaffinity purified MW 44 kDa (Ikeda et al., 2003). 0.0032 per GAPDH mRNA in adult human brain by RT-RT-PCR (Nishimura et al, 2003). 

Frequent inflammation of the pharynx and larynx has heen reported in exposed workers. Very small quantities of the dust have caused asthmatic attacks in workers after periods of exposure ranging from 3 months to 10 years. Sensitization dermatitis has heen reported from its use in the fur dyeing industry. In this process, oxidation products of p-phenylenedi-amine are generated that are also strong skin sensitizers. Many instances of inflammation and damage of periocular and ocular tissue have been reported from contact with hair dyes containing p-phenylenediamine, presumably in sensitized individuals. ... 

Ophthalmic ointments maintain contact between the drug and ocular tissues by slowing the clearance rate to as little as 0.5%/min. Ophthalmic ointments provide maximum contact between drug and external ocular tissues. 

The ointment is particularly convenient when an eye pad is used. It also may be the preparation of choice for patients in whom therapeutic benefit depends on prolonged contact of the active ingredients with ocular tissues. FLUOROMETHALONE Consult a physician if there is no improvement after 2 days. Do not discontinue therapy prematurely. In chronic conditions, withdraw treatment by gradually decreasing the frequency of applications. 

Chloramphenicol also is widely used for the topical treatment of eye infections. It is a very effective agent because of its extremely broad spectrum of activity and its ability to penetrate ocular tissue. The availability of safer, less irritating instilled ophthalmic antibiotics and the increase in fatal aplastic anemia associated with the use of this dosage form suggest that this agent might best be withdrawn. 

Table 12 shows the differences in penetration of ocular tissues of the different tamponade media [28]. 

Table 12. Penetration of ocular tissues of pig eyes in the result of a simulated eye surgery [28]...

Skin and Eye Irritation The solvent should not be a skin or eye irritant. A product is considered to be a skin irritant if it has a mean score of 2 or more for either erythema and eschar formation or edema formation, based on the OECD dermal scoring system (OECD, TG 404). A product is classified as an eye irritant if it causes significant ocular lesions, in any type of ocular tissue (i.e., cornea, iris, or conjuncti-vae) within 72 hours after exposure and which persist for at least 24 hours. 

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