Corneal abnormalities usually heal on their own, but untreated major damage can lead to inflammation, infection, ulceration, and even blindness.
According to researchers writing in The American Journal of Pathology, “a new study provides exciting evidence supporting the involvement of aquaporin in corneal cell proliferation and nerve regeneration, and suggests aquaporin 5 (AQP5) induction as a potential therapy to accelerate the resurfacing of corneal defects.”
The cornea, which is made up of transparent tissue in the eye’s outer layer, serves as a barrier to external stimuli. It is also important for eyesight.
“As a member of aquaporin family, AQP5 is expressed in the cornea, which is related to many eye diseases,” explained lead investigator Peng Chen, Ph.D., Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Shandong Province; and Institute of Stem Cell Regeneration Medicine, School of Basic Medicine, Qingdao University, Qingdao, China.
If a corneal injury is not treated quickly enough, pathogens can infiltrate the cornea, causing inflammation, turbidity, ulcers, and even blindness.
“In previous studies, we found that AQP5 deficiency can cause corneal epithelial punctate defects. There is also increasing evidence that nerve growth factor (NGF) plays a key role in corneal wound healing. AQP5 deficiency can slow down the repair of corneal epithelial injury in mice, but its specific mechanism remained unclear. We hypothesized that AQP5 plays an important role in one or more stages of corneal epithelial regeneration and explored the specific mechanism of AQP5.”
The researchers created an Aqp5 knockout (Aqp5-/-) animal model and performed corneal wound healing on corneas that had been scraped clean of epithelial cells. A total of 75 male Aqp5+/+ mice and 189 male Aqp5-/- mice aged 10 to 12 weeks were utilized in the study.
In previous studies, we found that AQP5 deficiency can cause corneal epithelial punctate defects. There is also increasing evidence that nerve growth factor (NGF) plays a key role in corneal wound healing. AQP5 deficiency can slow down the repair of corneal epithelial injury in mice, but its specific mechanism remained unclear. We hypothesized that AQP5 plays an important role in one or more stages of corneal epithelial regeneration and explored the specific mechanism of AQP5.
Peng Chen
The Aqp5-/- animals had a considerably longer time to corneal epithelial and nerve regeneration. NGF was injected into the subconjunctival area after the corneal epithelium was scraped off in Aqp5-/- mice to investigate its involvement in corneal epithelial damage healing.
The administration with NGF greatly increased the pace of epithelium and nerve regeneration in Aqp5-/- mice, as well as the recovery of corneal nerve fiber density and sensitivity in Aqp5-/- animals, accompanied by recovered levels of phosphorylated Akt.
The researchers also gave Aqp5-/- mice an Akt inhibitor in addition to NGF to figure out how NGF regulates the pace of corneal epithelial damage healing. The Akt inhibitor, on the other hand, inhibited the enhancement of NGF-induced corneal epithelial and nerve regeneration rates as well as Akt reactivation.
“It is exciting to find that Aqp5 deficiency can affect the nerve regeneration of mice by affecting the activation of NGF and Akt signaling pathways, which is not found in previous studies,” commented Dr. Chen.
“These results need to be confirmed in a clinical setting, but they provide evidence for the involvement of aquaporins in cell proliferation and nerve regeneration and suggest AQP5 induction as a possible therapy to accelerate the resurfacing of corneal defects.”
Aquaporins (AQPs), commonly known as water channels, are channel proteins that produce gaps in the membranes of living cells, allowing water to flow between them. They are found in the corneal epithelium.
In mammals, thirteen distinct kinds of AQPs have been discovered. They are important in maintaining cell water homeostasis since they are transmembrane proteins.
