Mapping the entire human corneal nerve architecture

Abstract

We developed an approach to generate a three-dimensional map that facilitates the assessment of epithelial nerve density in different corneal areas to define aging and gender influence on human corneal nerve architecture. Twenty-eight fresh human eyes from 14 donors of different ages were studied. Corneal nerves were stained and consecutive images acquired with a fluorescence microscope, recorded at the same plane, and merged for viewing the complete epithelial and stromal nerve architecture. After whole mount examination, the same cornea was also used for transection. Stromal nerves entered the cornea in a radial pattern, subsequently dividing into smaller branches. Some branches connected at the center of the stroma, but most penetrated upward into the epithelium. No differences were observed between nerve densities in the four corneal quadrants. Epithelial innervation in the limbal and most of the peripheral area was supplied by a superficial network surrounding the limbal area. Central epithelial nerves were supplied by branches of the stromal nerve network. Epithelial nerve density and terminal numbers were higher in the center of the cornea, rather than the periphery. There were no differences in epithelial nerve density between genders, but there was a progressive nerve density reduction concomitant with aging, mainly in eye samples of donors 70-years of age and older. The modified technique of tissue preparation used for this study allowed for observation of new nerve structure features and, for the first time, provided a complete view of the human corneal nerve architecture. Our study reveals that aging decreases the number of central epithelial nerve terminals, and increases the presence of irregular anomalies beneath the basal layer.

Short-Term Effects of Overnight Orthokeratology on Corneal Sub-basal Nerve Plexus Morphology and Corneal Sensitivity

“…In individuals wearing Seefree OK lenses, Langerhans cells were mainly observed in the midperipheral cornea and more rarely seen in central cornea, in agreement with the findings of others. 17,35 In both these areas, Langerhans cell density was greater after 1 month of treatment in this group. The immunological functions of dendritic cells and their role in corneal inflammation and dry eye disease have been well established.…”

“…Thus, only sensitivity and SBNP thickness data were available for the midperipheral cornea in control subjects: corneal sensitivity was 4.9460.42 cm at baseline and its change over the 1-month period was 20.0660.18 cm; SBNP thickness was 12.1161.27 mm and its change over the 1-month period was 0.3361.50 mm (P¼0. 35 …”

Cornea and its changes in diabetes mellitus: the review

“…В норме она прозрачная, не имеет кровеносных сосудов [8,9,10]. Роговица содержит более 7000 чувствительных нервных окончаний на 1 мм 2 , тогда как кожа -около 2000 на 1 мм 2 [11,12]. Для обеспечения достаточного питания эпителиального слоя на 2,1 млн ба-зальных клеток роговицы приходится до 1,4 млн нервных окончаний.…”

“…Авторами изучены 28 свежих роговиц человека 14 доноров раз-личного возраста. Установлено, что плотность НВР выше в центре роговицы по сравнению с периферией и снижается по мере старения, главным образом после 70 лет, нет разницы в плотности нервных волокон между четырьмя квадрантами роговицы, а также мужчинами и женщинами [12].…”

Comparative quantitative assessment of the human corneal sub-basal nerve plexus by in vivo confocal microscopy and histological staining

“…[14][15][16] IHC has been widely used in the field of ophthalmology to obtain comprehensive anatomical descriptions of human corneal nerve innervation patterns and architecture. [17][18][19] While recent advances in imaging by IVCM provide the opportunity to observe corneal nerves in extended areas ranging up to 18 mm 2 , 8 immunohistochemical staining of corneal whole mounts, by using an anti-neuronal class III β-tubulin primary antibody, offers visualization of the corneal nerve architecture from the entire central cornea (~6 mm in diameter). A recent study demonstrates that the average sub-basal nerve densities of standard in vivo confocal microscopic images are comparable to wide-field mapped composite images.…”