The effect of intrastromal PRP and oral doxycycline in corneal wound healing after alkali burn

PDF (English)
Опубликован: Feb 5, 2019
DOI: https://doi.org/10.12681/jhvms.16119
Glykeria Charalambidou
Aristotle University of Thessaloniki
Evangelia Kofidou
Aristotle University of Thessaloniki
Nikolaos Papaioannou
Aristotle University of Thessaloniki
Vasileios Karampatakis
Aristotle University of Thessaloniki
Anastasia Komnenou
Aristotle University of Thessaloniki
Аннотация

Ocular chemical burns are among the most critical and true ocular emergencies in dogs and cats, with destructive consequences on the ocular surface and intraocular tissues. Platelet alpha granules are an important reservoir of growth factors that can stimulate chemotaxis of inflammatory cells, mitosis, migration and differentiation of cells. On the other hand, tetracyclines and their derivatives exhibit non-antimicrobial properties, such as affecting inflammation, immunomodulation, cell proliferation and angiogenesis. The objective of this study is to investigate the effect of intrastromal platelet rich plasma (PRP) in combination with oral doxycycline in the healing process of the cornea. Thirty six New Zealand rabbits were used in this experimental study. Alkali burns were created by applying a round filter paper soaked in NaOH. PRP was prepared by centrifugation of autologous blood. The rabbits were allocated to four groups (9 animals each). Group 1 served as the control group without any treatment. Group 2 received doxycycline (5mg/kg b.w.) orally once a day throughout the study. Group 3 received an intrastromal injection of PRP (0.5ml) in the cornea, and group 4 received intrastromal PRP combined with oral doxycycline. Treatments had varied levels of success, with PRP combined with oral doxycycline producing the best results regarding corneal healing. Animals in the control group had epithelial defects for the whole duration of the study, and 3 animals presented corneal perforation. Groups 3 and 4 had smaller mean defect area, compared to groups 1 and 2. On the 7th day, neovascularisation was lower in treatment groups compared to the control group. Groups 3 and 4 also had less corneal oedema compared to the control group on day 3 and 7. Group 4 exhibited the best wound healing, with less neovascularization and better collagen arrangement, as shown by the histopathological evaluation. To the authors’ knowledge this is the first experimental study that intrastromal PRP is combined with oral doxycycline for the management of corneal chemical burns. This combination is a simple, safe and economical therapeutic approach that promotes corneal healing.

Article Details
  • Раздел
  • Research Articles
Лицензия Creative Commons

Это произведение доступно по лицензии Creative Commons «Attribution-NonCommercial» («Атрибуция — Некоммерческое использование») 4.0 Всемирная.

Authors who publish with this journal agree to the following terms:

· Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution Non-Commercial License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

· Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g. post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.

· Authors are permitted and encouraged to post their work online (preferably in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.

Скачивания
Данные скачивания пока недоступны.
Биографии авторов
Glykeria Charalambidou, Aristotle University of Thessaloniki
DVM, PhD Candidate, Comparative Ophthalmology Unit, Clinic of Companion Animals, School of Veterinary Medicine, Faculty of Health Sciences
Evangelia Kofidou, Aristotle University of Thessaloniki
Biologist, PhD Candidate, DVM Student, School of Veterinary Medicine, Faculty of Health Sciences
Nikolaos Papaioannou, Aristotle University of Thessaloniki
DVM, PhD, Professor, Laboratory of Pathology, School of Veterinary Medicine, Faculty of Health Sciences
Vasileios Karampatakis, Aristotle University of Thessaloniki
MD, PhD, Professor, Laboratory of Experimental Ophthalmology, School of Medicine, Faculty of Health Sciences
Anastasia Komnenou, Aristotle University of Thessaloniki
DVM, PhD, Associate Professor, Comparative Ophthalmology Unit, Clinic of Companion Animals, School of Veterinary Medicine, Faculty of Health Sciences
Библиографические ссылки
Abrams KL, Brooks DE, Funk RS, Theran P (1990) Evaluation of the Schirmer tear test in clinically normal rabbits. Am J Vet Res 51(12):1912-1913.
Alio J, Abad M, Artola A, Rodriguez-Prats JL, Pastor S, Ruiz-Colecha J (2007a) Use of Autologous Platelet-Rich Plasma in the Treatment of Dormant Corneal Ulcers. Ophthalmology 114(7):1286–1294.
Alio J, Rodriguez AE, WróbelDudzinska D (2015) Eye platelet-rich plasma in the treatment of ocular surface disorders. Curr Opin Ophthalmol 26(4):325–332.
Alio J, Colecha JR, Pastor S, Rodriguez A, Artola A (2007b) Symptomatic dry eye treatment with autologous platelet-rich plasma. Ophthalmic Res 39(3):124–129.
Almaliotis D, Koliakos G, Papakonstantinou E, Komnenou A, Thomas A, Petrakis S, Nakos I, Gounari E, Karampatakis V (2015) Mesenchymal stem cells improve healing of the cornea after alkali injury. Graefe’s Arch Clin Exp Ophthalmol 253(7):1121–1135.
Ambati BK, Joussen AM, Ambati J, Moromizato Y, Guha C, Javaherian K, Gillies S, O'Reilly MS, Adamis AP (2002) Angiostatin inhibits and regresses corneal neovascularization. Arch Ophthalmol 120(8):1063–1068.
ARVO, Association for Research in Vision and Ophthalmology (2016) Statement for the use of animals in ophthalmic and visual research. Available at: https://www.arvo.org/About/policies/statement-for-the-use-of-animals-in-ophthalmic-and-vision-research [Accessed May 23 2017].
El Attar T, Lin HS, Shultz R (1988) Effect of minocycline on prostaglandin formation in gingival fibroblasts. J Periodontal Res 23(5):285–286.
Bakunowicz-łazarczyk A, Urban B (2016) Advances in Medical Sciences Assessment of therapeutic options for reducing alkali burn-induced corneal neovascularization and inflammation. Adv Med Sci 61(1):101–112.
Bisla K, Tanelian DL (1992) Concentration-Dependent Effects of Lidocoine on Corneol Epithelial Wound Healing. Investig Ophthalmol Vis Sci 33(11):3029–3033.
Borzini P, Mazzucco L (2005) Tissue regeneration and in loco administration of platelet derivatives: Clinical outcome, heterogeneous products, and heterogeneity of the effector mechanisms. Transfusion 45(11):1759–1767.
Burns FR, Stack SM, Gray RD, Parerson CA (1989) Inhibition of Purified Collogenose from Alkali-Burned Rabbit Corneas. Investig Ophthalmol Vis Sci 30(7):1569–1575.
Busse C, Hartley C, Kafarnik C, Pivetta M (2014) Ocular alkaline injury in four dogs - presentation, treatment, and follow-up - a case series. Vet Ophthalmol 18(2):127–134.
Christmas R (1991) Management of chemical burns of the canine cornea. Can Vet J 32(10):608–612.
Chung JH, Kim HJ, Fagerholmb, Cho BC (1996) Effect of topically applied Na-hyaluronan on experimental corneal alkali wound healing. Korean J Ophthalmol 10(2):68–75.
Crum R, Szabo S, Folkman J (1985) A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment. Science 230(4732):1375–1378.
Dan L, Shi-long Y, Miao-li L, Yong-ping L, Hong-jie M, Ying Z, Xiang-gui W (2008) Inhibitory effect of oral doxycycline on neovascularization in a rat corneal alkali burn model of angiogenesis. Curr Eye Res 33(8):653–60.
Dua HS, King AJ, Joseph A (2001) A new classification of ocular surface burns. Br J Ophthalmol 85(11):1379–83.
Efeoglu C, Akçay YD, Ertürk S (2004) A modified method for preparing platelet-rich plasma: An experimental study. J Oral Maxillofac Surg 62(11):1403–1407.
Federici TJ (2011) The non-antibiotic properties of tetracyclines: Clinical potential in ophthalmic disease. Pharmacol Res 64(6):614–623.
Fish R, Davidson RS (2010) Management of ocular thermal and chemical injuries, including amniotic membrane therapy. Curr Opin Ophthalmol 21(4):317–321.
Frechette JP, Martineau I, Gagnon G (2005) Platelet-rich plasmas: growth factor content and roles in wound healing. J Dent Res 84(5):434–439.
Geremicca W, Fonte C, Vecchio S (2010) Blood components for topical use in tissue regeneration: Evaluation of corneal lesions treated with platelet lysate and considerations on repair mechanisms. Blood Transfus 8(2):107–112.
Gimeno LF, Gatto SC, Croxatto JO, Ferro JI, Gallo JE (2010) In vivo lamellar keratoplasty using platelet-rich plasma as a bioadhesive. Eye 24(2):368–375.
Gimeno LF, Gatto SC, Ferro J, Croxatto JO, Gallo JE (2006) Preparation of platelet-rich plasma as a tissue adhesive for experimental transplantation in rabbits. Thromb J 4(18):1-7.
Gunay C, Sagliyan A, Yilmaz S, Kandemir FM, Han MC, Ozkaraca M, Kulualp K (2015) Evaluation of autologous serum eyedrops for the treatment of experimentally induced corneal alcali burns. Rev Med Vet (Toulouse) 166(3-4):63–71.
Joussen AM, Kruse FE, Volcker HE, Kirchhof B (1999) Topical application of methotrexate for inhibition of corneal angiogenesis. Graefe’s Arch Clin Exp Ophthalmol 237(11):920–927.
Khaksar E, Aldavood SJ, Abedi GR, Sedaghat R, Nekoui O, Zamani-ahmadmahmudi M (2013) The effect of sub-conjunctival platelet-rich plasma in combination with topical acetylcysteine on corneal alkali burn ulcer in rabbits. Comp Clin Path 22(1):107–112.
Kuo IC (2004) Corneal wound healing. Curr Opin Ophthalmol 15(4):311–315.
Levinson RA, Paterson CA, Pfister RR (1976) Ascorbic acid prevents corneal ulceration and perforation following experimental alkali burns. Invest Ophthalmol 15(12):986–993.
Márquez-de-Aracena R, Montero-de-Espinosa I, Munoz M, Pereira G (2007) Subconjunctival application of plasma platelet concentrate in the treatment of ocular burns. Preliminary results. Arch Soc Esp Oftalmol 82:475–481.
McCulley PJ (1987) Chemical injuries. In: Smolin G, Thoft AR eds. The cornea. Boston, Mass, Little, Brown and Co: pp 527–542.
Nip LH, Uitto VJ, Golub LM (1993) Inhibition of epithelial cell matrix metalloproteinases by tetracyclines. J Periodont Res 28(5):379–385.
Nurden AT (2011) Platelets, inflammation and tissue regeneration. Thromb Haemost Suppl 105(1):13–33.
Perry HD, Hodes LW, Seedor JA, Donnenfeld ED, McNamara TF, Golub LM (1993) Effect of doxycycline hyclate on corneal epithelial wound healing in the rabbit alkali-burn model. Preliminary observations. Cornea, 12(5):379–382.
Peyman GA, Kivilcim M, Morales AM, DellaCroce JT, Conway MD (2007) Inhibition of corneal angiogenesis by ascorbic acid in the rat model. Graefe’s Arch Clin Exp Ophthalmol 245(10):1461–1467.
Pfister RR, Haddox JL, Lank KM (1988) Citrate or ascorbate/citrate treatment of established corneal ulcers in the alkali-injured rabbit eye. Investig Ophthalmol Vis Sci 29(7):1110–1115.
Ramamurthy NS, Vernillo AT, Greenwald RA, Lee HM, Sorsa T, Golub LM, Rifkin BR (1993) Reactive oxygen species activate and tetracyclines inhibit rat osteoblast collagenase. J bone Miner Res 8(10):1247–1253.
Salman IA, Gundogdu C (2010) Epithelial healing in experimental corneal alkali wounds with nondiluted autologous serum eye drops. Cutan Ocul Toxicol 29(2):116–121.
Sanchez Mejia RO, Ona VO, Li M, Friedlander RM (2001) Minocycline reduces traumatic brain injury-mediated caspase-1 activation, tissue damage, and neurological dysfunction. Neurosurgery 48(6):1393–1401.
Sapadin AN, Fleischmajer R (2006) Tetracyclines: Nonantibiotic properties and their clinical implications. J Am Acad Dermatol 54(2):258–265.
Schultz G, Chegini N, Grant M, Khaw P, MacKay S (1992) Effects of Growth Factors on Corneal Wound Healing. Acta Ophthalmol 70(S202):60–66.
Seedor JA, Perry HD, McNamara TF, Golub LM, Buxton DF, Guthrie DS (1987) Systemic tetracycline treatment of alkali-induced corneal ulceration in rabbits. Arch Ophthalmol 105(2):268–271.
Şenel OO, Ergİn İ (2014) Medical and surgical treatment of severe corneal alkaline burn in a cat. Vet Hekimler Dern Dergisi, J Vet Med Soc 85(1):24–28.
Singh P, Tyagi M, Kumar Y, Gupta KK, Sharma PD (2013) Ocular chemical injuries and their management. Oman J Ophthalmol 6(2):83–87.
Sorsa T, Konttinen YT, Lindy O, Suomalainen K, Ingman T, Halinen S, Lee HM, Golub LM, Hall J (1993) Doxycycline protects serum alpha-1-antitrypsin from human neutrophil collagenase. Agents Actions Suppl 39:225–229.
Stuart JC, Turgeon P, Kowalski RP (1989) Use of aprotinin in the treatment of pseudomonas corneal ulceration. Trans Pa Acad Ophthalmol Otolaryngol 41:823–826.
Suomalainen K, Sorsa T, Ingman T, Lindy O, Golub LM 1(992) Tetracycline inhibition identifies the cellular origin of interstitial collagenases in human periodontal diseases in vivo. Oral Microbiol Immunol 7(2):121–123.
Swank A, Hosgood G (1996) Healing and the role of growth factors. Compend Small Anim 18(9):1007–1016.
Tanidir ST, Yuksel N, Altintas O, Yildiz DK, Sener E, Caglar Y (2010) The effect of subconjunctival platelet-rich plasma on corneal epithelial wound healing. Cornea 29(6):664–669.
Uckun OM, Alagoz F, Secer M, Karakoyun O, Ocakcioglu A, Yildirim AE, Yimaz F, Sahinoglu M, Divanlioglu D, Dalgic A, Daglioglu E, Belen AD (2015) Neuroprotective effects of tetracyclines on blunt head trauma: An experimental study on rats. J Neurosci Rural Pract 6(1):27–32.
Vadas P, Greenwald RA, Stree RT, Pruzanski W (1991) Inhibition of synovial fluid phospholipase A2 activity by 2 tetracycline derivatives, minocycline and doxycycline. Arthriti Rheum 34(1):51-60.
Wagoner MD (1997) Chemical injuries of the eye: Current concepts in pathophysiology and therapy. Surv Ophthalmol 41(4):275–313.
Williams DL, Barrie K, Evans TF (2002) Cornea. In: Veterinary Ocular Emergencies. Butterworth-Heinemann, Edinburgh: pp 37–63.