1 / 14

Report of the Neurobiology Subcommittee Members: Fiona Stapleton (Co-Chair & SC Liason)

Report of the Neurobiology Subcommittee Members: Fiona Stapleton (Co-Chair & SC Liason) Carl Marfurt Blanka Golebiowski Mark Rosenblatt (Co-Chair) David Bereiter Carolyn Begley Darlene Dartt Juana Gallar Carlos Belmonte Pedram Hamrah Mark Willcox (Harmonization Subcommittee).

adeola
Download Presentation

Report of the Neurobiology Subcommittee Members: Fiona Stapleton (Co-Chair & SC Liason)

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Report of the Neurobiology Subcommittee Members: Fiona Stapleton (Co-Chair & SC Liason) Carl Marfurt Blanka Golebiowski Mark Rosenblatt (Co-Chair) David Bereiter Carolyn Begley Darlene Dartt Juana Gallar Carlos Belmonte Pedram Hamrah Mark Willcox (Harmonization Subcommittee)

  2. Neurobiology Subcommittee Scope: • Anatomy and morphological characteristics • Molecular and cellular neurobiology of ocular discomfort and pain. • Limited data on neurobiology of CL wear, evidence generated for dry eye disease was examined. • Inflammatory pathway, impact of hyperosmolarity, peripheral and central mediators of ocular sensation. • Stimulus delivered by CL & how this might impact those peripheral and central processes • Neurobiological view of potential treatments. • Areas of future research identified.

  3. Neurobiology Subcommittee Sensory nerves: • Area of the ocular surface which interacts with the CL • Anatomy, morphology and neurochemistry • Corneal innervation is well characterised; limited information on conjunctiva & eyelid margin1,2 • Human corneal sensory neuropeptides predominantly CGRP & substance P3 • No evidence yet that CLD impacts morphology or neurochemistry

  4. Neurobiology Subcommittee Neurophysiology & sensation - PNS: • Functional types of ocular sensory neurons4 • Polymodalnociceptors (70%) • Mechano-nociceptors (15-20%) • Cold-sensitive receptors (10-15%) • Sensitisation of polymodal & cold nociceptors • Transduction /coding of stimuli modulated by many ion channels5 • Transient Receptor Protein (TRP) Channels – polymodal activation • Others ; Acid Sensing Ion Channels (ASICs) and K+ channels

  5. Neurobiology Subcommittee Neurophysiology & sensation - PNS: • Relationship with sensation? • Ion channels not functionally associated with nociceptor type5 • Stimulus is encoded based on combination of different ion channels in each neuronal type • Abnormal peripheral signalling may occur with persistent stimulation or inflammation - conceivable in CLD. • Evidence in CLD limited. Increased conjunctival mechanical sensitivity in symptomatic CL wear6; altered response to suprathreshold stimuli7

  6. Neurobiology Subcommittee Neurophysiology & sensation: CNS: • Complex nature of perceptions suggests integration at higher brain centres

  7. Neurobiology Subcommittee Summary of the neurophysiology of CLD

  8. Neurobiology Subcommittee Treatments (neurobiological targets): • Reduce mechanical stimulation • Alter materials, change friction modulus8,9 • Reduce mechanical insult to the conjunctiva9 • Chemical • Reduce activation/sensitization of polymodal nociceptors10 • Control pH & osmolarity known to activate receptors11 • Limit dehydration12 • Pharmacological agents • Neuropathic pain, altered excitability of corneal nerves13 • Others, e.g. NGF to treat nerve architecture or αNGF manage symptomatology14

  9. Neurobiology Subcommittee Future directions for research: • Pain/discomfort questionnaires • Morphological and functional studies • Animal Models • Contact lens wear • Pain models • Natural history or chronicity of discomfort

  10. Neurobiology Subcommittee Summary: • Corneal nerves only well studied • Current understanding of ocular surface sensation is incomplete • Relevant aspects of CL wear in CLD: • physical interaction with ocular surface • hyperosmolarity • chemical mediators in MPS/packaging solutions • inflammatory mediators • Sensory changes due to neural adaptation to a continuous stimulus or neural sensitization in response to hyperosmolarity or inflammatory mediators

  11. Neurobiology Subcommittee Summary: • Future directed treatments • Lens related factors • Agents to modulate peripheral & central nervous system responses • Development of sensitive measurement & analytical techniques at all stages of discomfort pathway.

  12. Thank you! QUESTIONS?

  13. Neurobiology Subcommittee Key References: • Al-Aqaba MA, Fares U, Suleman H, Lowe J, Dua HS. Architecture and distribution of human corneal nerves. Br J Ophthalmol 2010;94:784-789. • Bron AJ, Tripathi, R., and Tripathi, B. Wolff's Anatomy of the Eye and Orbit. 8th ed. London: Chapman and Hall Medical; 1997. • Marfurt CF. Peptidergic innervation of the cornea: anatomical and functional consideration. In: Troger JaK, G. (ed), Neuropeptides in the Eye. Kerala: Research Signpost; 2009:23-37. • Belmonte C, Aracil A, Acosta MC, Luna C, Gallar J. Nerves and sensations from the eye surface. Ocul Surf 2004;2:248-253. • Viana F, Belmonte C. Transduction and encoding of noxious stimulus. In: Schmidt RF, Gebhart GF (eds), Encyclopedia of Pain: Springer; 2013. • Tan et al., IOVS 1997; 38 ARVO abstract S1336 • Chen J, Simpson TL. A role of corneal mechanical adaptation in contact lens-related dry eye symptoms. Invest Ophthalmol Vis Sci 2011;52:1200-1205. • Holden BA, Stephenson A, Stretton S, et al. Superior epithelial arcuate lesions with soft contact lens wear. Optom Vis Sci 2001;78:9-12.

  14. Neurobiology Subcommittee Key References: • Santodomingo-Rubido J, Wolffsohn J, Gilmartin B. Conjunctival epithelial flaps with 18 months of silicone hydrogel contact lens wear. Eye Contact Lens 2008;34:35-38. • Lazon de la Jara P, Papas E, Diec J et al. Effect of lens care systems on the clinical performance of a contact lens. Optom Vis Sci 2013;90:344-350. • Stahl U, Willcox M, Stapleton F. Role of hypo-osmotic saline drops in ocular comfort during contact lens wear. Contact Lens Ant Eye 2010;33:68-75. • Peterson RC, Wolffson JS, Nick J et al. Clinical performance of daily disposable soft contact lenses using sustained release technology. Contact Lens Ant Eye 2006;29:137-134. • Lichtinger A, Purcell TL, Schanzlin DJ, Chayet AS. Gabapentin for postoperative pain after photorefractive keratectomy: a prospective, randomized, double-blind, placebo-controlled trial. J Refract Surg 2011;27:613-617. • Eibl JK, Strasser BC, Ross GM. Structural, biological, and pharmacological strategies for the inhibition of nerve growth factor. Neurochem Int 2012;61:1266-1275.

More Related