Ex vivo confocal microscopy of human corneal nerves

Al-Aqaba, Mouhamed; Alomar, Thaer; Miri, Ammar; Fares, Usama; Otri, Ahmad Muneer; Dua, H S

doi:10.1136/bjo.2009.178244

Cited by 38 publications

(24 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the presence of A␦-fibers was also assessed via the examination of images from the stromal layer, although in this study an exact quantification was not performed due to current methodological limitations (Patel and McGhee 2009). Stromal rather than subbasal nerves appear more robust in surviving postmortem change; therefore, most of our knowledge from corneal A ␦-fibers is from in vitro studies (Al-Aqaba et al 2010).…”

Section: Methodsmentioning

confidence: 99%

“…C-fibers are mainly located in the subbasal plexus between the Bowman's layer and the corneal basal epithelium, whereas A␦-fibers are located in the stromal layer (Guthoff et al 2005;Muller et al 1997). Each main fiber is constituted of a bundle of unmyelinated axons (Al-Aqaba et al 2010). Three corneal nerve parameters were quantified from the subbasal plexus: 1) corneal nerve fiber density (CNFD), the total number of main fibers per square millimeter of corneal tissue (Al-Aqaba et al 2010); 2) corneal nerve branch density (CNBD), the number of branches emanating from all main fibers trunks per square millimeter of corneal tissue; and 3) corneal nerve fiber length (CNFL), the total length of all main fibers and branches (mm/mm 2 ) within the area of corneal tissue.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Rare human nerve growth factor-β mutation reveals relationship between C-afferent density and acute pain evaluation

Perini

Tavakoli

Marshall

et al. 2016

Journal of Neurophysiology

View full text Add to dashboard Cite

Perini I, Tavakoli M, Marshall A, Minde J, Morrison I. Rare human nerve growth factor-␤ mutation reveals relationship between C-afferent density and acute pain evaluation. J Neurophysiol 16: 425-430, 2016. First published May 4, 2016 doi:10.1152/jn.00667.2015The rare nerve growth factor-␤ (NGFB) mutation R221W causes a selective loss of thinly myelinated fibers and especially unmyelinated C-fibers. Carriers of this mutation show altered pain sensation. A subset presents with arthropathic symptoms, with the homozygous most severely affected. The aim of the present study was to investigate the relationship between peripheral afferent loss and pain evaluation by performing a quantification of small-fiber density in the cornea of the carriers, relating density to pain evaluation measures. In vivo corneal confocal microscopy (CCM) was used to quantify C-fiber loss in the cornea of 19 R221W mutation carriers (3 homozygous) and 19 age-matched healthy control subjects. Pain evaluation data via the Situational Pain Questionnaire (SPQ) and the severity of neuropathy based on the Neuropathy Disability Score (NDS) were assessed. Homozygotes, heterozygotes, and control groups differed significantly in corneal C-nerve fiber density, with the homozygotes showing a significant afferent reduction. Importantly, peripheral C-fiber loss correlated negatively with pain evaluation, as revealed by SPQ scores. This study is the first to investigate the contribution of small-fiber density to the perceptual evaluation of pain. It demonstrates that the lower the peripheral small-fiber density, the lower the degree of reported pain intensity, indicating a functional relationship between small-fiber density and higher level pain experience.nerve growth factor-␤ gene mutation; corneal confocal microscopy; pain evaluation; Situational Pain Questionnaire; C-fiber NEW & NOTEWORTHY

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Rare human nerve growth factor-β mutation reveals relationship between C-afferent density and acute pain evaluation

Perini

Tavakoli

Marshall

et al. 2016

Journal of Neurophysiology

View full text Add to dashboard Cite

show abstract

“…As these nerve bundles travel, they undergo division into smaller branches to innervate the anterior and mid stroma, and eventually turn 908 toward the surface, perforating Bowman's layer. 7 They then turn again 908 to travel between Bowman's layer and the basal epithelial cells forming the subbasal nerve plexus. From there the individual subbasal nerves give branches to innervate the more superficial epithelial cells.…”

mentioning

confidence: 99%

Early Corneal Nerve Damage and Recovery Following Small Incision Lenticule Extraction (SMILE) and Laser In Situ Keratomileusis (LASIK)

Mohamed-Noriega

Riau

Lwin

et al. 2014

Invest. Ophthalmol. Vis. Sci.

107

View full text Add to dashboard Cite

show abstract

“…Neuroexplorer software (Nex Technologies, Littleton, MA) was used to measure the total length of stromal nerves and the area of the contour in which nerves had been traced. Corneal nerve fiber density (NFD) was calculated by dividing the total length of nerve fibers (mm) by the area of the contour (mm 2 ) as described by Al-Aqaba et al 17 …”

Section: Stereofluorescence Imagingmentioning

confidence: 99%

Corneal Neurotoxicity Due to Topical Benzalkonium Chloride

Sarkar¹,

Chaudhary²,

Namavari³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

123

View full text Add to dashboard Cite

PURPOSE. The aim of this study was to determine and characterize the effect of topical application of benzalkonium chloride (BAK) on corneal nerves in vivo and in vitro.METHODS. Thy1-YFP+ neurofluorescent mouse eyes were treated topically with vehicle or BAK (0.01% or 0.1%). Widefield stereofluorescence microscopy was performed to sequentially image the treated corneas in vivo every week for 4 weeks, and changes in stromal nerve fiber density (NFD) and aqueous tear production were determined. Whole-mount immunofluorescence staining of corneas was performed with antibodies to axonopathy marker SMI-32. Western immunoblot analyses were performed on trigeminal ganglion and corneal lysates to determine abundance of proteins associated with neurotoxicity and regeneration. Compartmental culture of trigeminal ganglion neurons was performed in Campenot devices to determine whether BAK affects neurite outgrowth.RESULTS. BAK-treated corneas exhibited significantly reduced NFD and aqueous tear production, and increased inflammatory cell infiltration and fluorescein staining at 1 week (P < 0.05). These changes were most significant after 0.1% BAK treatment. The extent of inflammatory cell infiltration in the cornea showed a significant negative correlation with NFD. Sequential in vivo imaging of corneas showed two forms of BAK-induced neurotoxicity: reversible neurotoxicity characterized by axonopathy and recovery, and irreversible neurotoxicity characterized by nerve degeneration and regeneration. Increased abundance of beta III tubulin in corneal lysates confirmed regeneration. A dose-related significant reduction in neurites occurred after BAK addition to compartmental cultures of dissociated trigeminal ganglion cells. Although both BAK doses (0.0001% and 0.001%) reduced nerve fiber length, the reduction was significantly more with the higher dose (P < 0.001).CONCLUSION. Topical application of BAK to the eye causes corneal neurotoxicity, inflammation, and reduced aqueous tear production. (Invest Ophthalmol Vis Sci.

show abstract

Ex vivo confocal microscopy of human corneal nerves

Cited by 38 publications

References 31 publications

Rare human nerve growth factor-β mutation reveals relationship between C-afferent density and acute pain evaluation

Rare human nerve growth factor-β mutation reveals relationship between C-afferent density and acute pain evaluation

Early Corneal Nerve Damage and Recovery Following Small Incision Lenticule Extraction (SMILE) and Laser In Situ Keratomileusis (LASIK)

Corneal Neurotoxicity Due to Topical Benzalkonium Chloride

Contact Info

Product

Resources

About